WO2026003586A2 - Vaccins à base d'herpèsvirus à sous-unités multiples et agents thérapeutiques - Google Patents

Vaccins à base d'herpèsvirus à sous-unités multiples et agents thérapeutiques

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Publication number
WO2026003586A2
WO2026003586A2 PCT/IB2025/000388 IB2025000388W WO2026003586A2 WO 2026003586 A2 WO2026003586 A2 WO 2026003586A2 IB 2025000388 W IB2025000388 W IB 2025000388W WO 2026003586 A2 WO2026003586 A2 WO 2026003586A2
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WIPO (PCT)
Prior art keywords
peptide
glycoprotein
nucleic acid
multisubunit
sequence
Prior art date
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Pending
Application number
PCT/IB2025/000388
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English (en)
Other versions
WO2026003586A3 (fr
Inventor
Tushar Ranjan MOHARANA
Soham Govindarajan SANKARAN
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Popvax Pvt Ltd
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Popvax Pvt Ltd
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Publication of WO2026003586A2 publication Critical patent/WO2026003586A2/fr
Publication of WO2026003586A3 publication Critical patent/WO2026003586A3/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • A61P31/22—Antivirals for DNA viruses for herpes viruses
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/53—DNA (RNA) vaccination
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55555—Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/70—Multivalent vaccine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/50—Fusion polypeptide containing protease site
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/80—Fusion polypeptide containing a DNA binding domain, e.g. Lacl or Tet-repressor
    • C07K2319/81—Fusion polypeptide containing a DNA binding domain, e.g. Lacl or Tet-repressor containing a Zn-finger domain for DNA binding
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/16011—Herpesviridae
    • C12N2710/16111—Cytomegalovirus, e.g. human herpesvirus 5
    • C12N2710/16122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/16011—Herpesviridae
    • C12N2710/16111—Cytomegalovirus, e.g. human herpesvirus 5
    • C12N2710/16134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/16011—Herpesviridae
    • C12N2710/16211—Lymphocryptovirus, e.g. human herpesvirus 4, Epstein-Barr Virus
    • C12N2710/16222—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/16011—Herpesviridae
    • C12N2710/16211—Lymphocryptovirus, e.g. human herpesvirus 4, Epstein-Barr Virus
    • C12N2710/16234—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/16011—Herpesviridae
    • C12N2710/16511—Roseolovirus, e.g. human herpesvirus 6, 7
    • C12N2710/16522—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/16011—Herpesviridae
    • C12N2710/16511—Roseolovirus, e.g. human herpesvirus 6, 7
    • C12N2710/16534—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/16011—Herpesviridae
    • C12N2710/16611—Simplexvirus, e.g. human herpesvirus 1, 2
    • C12N2710/16622—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/16011—Herpesviridae
    • C12N2710/16611—Simplexvirus, e.g. human herpesvirus 1, 2
    • C12N2710/16634—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/16011—Herpesviridae
    • C12N2710/16711—Varicellovirus, e.g. human herpesvirus 3, Varicella Zoster, pseudorabies
    • C12N2710/16722—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/16011—Herpesviridae
    • C12N2710/16711—Varicellovirus, e.g. human herpesvirus 3, Varicella Zoster, pseudorabies
    • C12N2710/16734—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Definitions

  • herpesviruses More than 100 herpesviruses are known, of them 8 herpesviruses (herpes simplex virus types 1 and 2, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, human herpesvirus 6, human herpesvirus 7, and Kaposi’s sarcoma-associated herpesvirus or human herpesvirus 8) routinely infect humans. It is said that all humans become infected with one or more herpesviruses during their lifetime.
  • herpesviruses herpes simplex virus types 1 and 2, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, human herpesvirus 6, human herpesvirus 7, and Kaposi’s sarcoma-associated herpesvirus or human herpesvirus
  • Herpesviruses cause a variety of diseases, for example, gingivostomatitits, genital herpes, herpetic keratitis, herpetic whitlows, neonatal herpes simplex virus infection, herpes simplex encephalitis, varicella or chickenpox, herpes zoster or shingles, congenital cytomegalic inclusion disease, cytomegalovirus mononucleosis, Epstein-Barr virus mononucleosis, exanthem subitem or roseola, and Kaposi sarcoma.
  • HSV1 and HSV2 alone have been estimated to have infected 3.7 billion and 491 million people globally under the age of 50 respectively.
  • herpesviruses After the primary infection, herpesviruses remain in the body in the latent form. Reactivation from latency is a major clinical concern in those individuals whose immune system is suppressed. Prophylactic and therapeutic interventions exist against the diseases caused by some of the herpesviruses, but they are inadequate. Therefore, effective vaccines and therapeutics against herpesviruses are an important necessity.
  • the present disclosure relates to a multisubunit nucleic acid comprising a plurality of polynucleotide sequences, wherein some or all polynucleotide sequences of the plurality comprises either a target sequence, a linker sequence, and a selfassembling sequence or a linker sequence, a target sequence, a linker sequence, and a selfassembling sequence or a combination thereof, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • each polynucleotide sequence of the plurality is connected to an adjacent polynucleotide sequence of the plurality by a cleavage sequence.
  • the multisubunit nucleic acid further comprises a signal sequence upstream of one or more of the polynucleotide sequences of the plurality.
  • the target sequence, the linker sequence, and the self-assembling sequence or the linker sequence, the target sequence, the linker sequence, and the self-assembling sequence are in 5' to 3' order.
  • a multisubunit nucleic acid comprising a plurality of polynucleotide sequences, wherein each polynucleotide sequence of the plurality comprises a target sequence, a linker sequence, and a self-assembling sequence, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • each polynucleotide sequence of the plurality is connected to an adjacent polynucleotide sequence of the plurality by a cleavage sequence.
  • the multisubunit nucleic acid further comprises a signal sequence upstream of one or more of the polynucleotide sequences of the plurality.
  • the target sequence, the linker sequence, and the self- assembling sequence are in 5' to 3' order.
  • a multisubunit nucleic acid comprising a plurality of polynucleotide sequences, wherein each polynucleotide sequence of the plurality comprises a linker sequence, a target sequence, a linker sequence, and a selfassembling sequence, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • each polynucleotide sequence of the plurality is connected to an adjacent polynucleotide sequence of the plurality by a cleavage sequence.
  • the multisubunit nucleic acid further comprises a signal sequence upstream of one or more of the polynucleotide sequences of the plurality.
  • the linker sequence, the target sequence, the linker sequence, and the self-assembling sequence are in 5' to 3' order.
  • a vaccine comprising a multisubunit nucleic acid, wherein the multisubunit nucleic acid comprises a plurality of polynucleotide sequences, wherein some or all polynucleotide sequences of the plurality comprises either a target sequence, a linker sequence, and a self-assembling sequence or a linker sequence, a target sequence, a linker sequence, and a self-assembling sequence, or a combination thereof, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • each polynucleotide sequence of the plurality is connected to an adjacent polynucleotide sequence of the plurality by a cleavage sequence.
  • the multisubunit nucleic acid further comprises a signal sequence upstream of one or more of the polynucleotide sequences of the plurality.
  • the target sequence, the linker sequence, and the selfassembling sequence or the linker sequence, the target sequence, the linker sequence, and the self- assembling sequence are in 5' to 3' order.
  • a vaccine comprising a multisubunit nucleic acid, wherein the multisubunit nucleic acid comprises a plurality of polynucleotide sequences, wherein each polynucleotide sequence of the plurality comprises a target sequence, a linker sequence, and a self-assembling sequence, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • each polynucleotide sequence of the plurality is connected to an adjacent polynucleotide sequence of the plurality by a cleavage sequence.
  • the multisubunit nucleic acid further comprises a signal sequence upstream of one or more of the polynucleotide sequences of the plurality.
  • the target sequence, the linker sequence, and the self-assembling sequence are in 5' to 3' order.
  • a vaccine comprising a multisubunit nucleic acid, wherein the multisubunit nucleic acid comprises a plurality of polynucleotide sequences, wherein each polynucleotide sequence of the plurality comprises a linker sequence, a target sequence, a linker sequence, and a self-assembling sequence, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • each polynucleotide sequence of the plurality is connected to an adjacent polynucleotide sequence of the plurality by a cleavage sequence.
  • the multisubunit nucleic acid further comprises a signal sequence upstream of one or more of the polynucleotide sequences of the plurality.
  • the linker sequence, the target sequence, the linker sequence, and the selfassembling sequence are in 5' to 3' order.
  • a multisubunit nucleic acid encoding a plurality of polypeptides, wherein some or all polypeptides of the plurality comprises either a target peptide, a linker peptide, and a self-assembling peptide or a linker peptide, a target peptide, a linker peptide, and a self- assembling peptide, or a combination thereof, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • each polypeptide of the plurality is connected to an adjacent polypeptide of the plurality by a cleavage peptide.
  • the multisubunit nucleic acid further encodes a signal peptide on the aminoterminus of one or more of the polypeptides of the plurality.
  • the target peptide, the linker peptide, and the self-assembling peptide or the linker peptide, the target peptide, the linker peptide and the self-assembling peptide are in N-terminus to C- terminus order.
  • each polypeptide of the plurality comprises a target peptide, a linker peptide, and a self-assembling peptide, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • each polypeptide of the plurality is connected to an adjacent polypeptide of the plurality by a cleavage peptide.
  • the multisubunit nucleic acid further encodes a signal peptide on the amino-terminus of one or more of the polypeptides of the plurality.
  • the target peptide, the linker peptide, and the selfassembling peptide are in N-terminus to C-terminus order.
  • each polypeptide of the plurality comprises a linker peptide, a target peptide, a linker peptide, and a self-assembling peptide, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • each polypeptide of the plurality is connected to an adjacent polypeptide of the plurality by a cleavage peptide.
  • the multisubunit nucleic acid further encodes a signal peptide on the amino-terminus of one or more of the polypeptides of the plurality.
  • the linker peptide, the target peptide, the linker peptide, and the self-assembling peptide are in N-terminus to C-terminus order.
  • a vaccine comprising a multisubunit nucleic acid encoding a plurality of polypeptides, wherein some or all polypeptides of the plurality comprises either a target peptide, a linker peptide, and a self-assembling peptide or a linker peptide, a target peptide, a linker peptide, and a self- assembling peptide or a combination thereof, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • each polypeptide of the plurality is connected to an adjacent polypeptide of the plurality by a cleavage peptide.
  • the multisubunit nucleic acid further encodes a signal peptide on the amino-terminus of one or more of the polypeptides of the plurality.
  • the target peptide, the linker peptide, and the self-assembling peptide or the linker peptide, the target peptide, the linker peptide and the self- assembling peptide are in N-terminus to C-terminus order.
  • a vaccine comprising a multisubunit nucleic acid encoding a plurality of polypeptides, wherein each polypeptide of the plurality comprises a target peptide, a linker peptide, and a self-assembling peptide, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • each polypeptide of the plurality is connected to an adjacent polypeptide of the plurality by a cleavage peptide.
  • the multisubunit nucleic acid further encodes a signal peptide on the amino-terminus of one or more of the polypeptides of the plurality.
  • the target peptide, the linker peptide, and the self- assembling peptide are in N-terminus to C-terminus order.
  • a vaccine comprising a multisubunit nucleic acid encoding a plurality of polypeptides, wherein each polypeptide of the plurality comprises a linker peptide, a target peptide, a linker peptide, and a self-assembling peptide, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • each polypeptide of the plurality is connected to an adjacent polypeptide of the plurality by a cleavage peptide.
  • the multisubunit nucleic acid further encodes a signal peptide on the aminoterminus of one or more of the polypeptides of the plurality.
  • the linker peptide, the target peptide, the linker peptide, and the self-assembling peptide are in N-terminus to C-terminus order.
  • total number of the polynucleotide sequences are not more than 100. In some embodiments, total number of the polynucleotide sequences are between 2-5, 2-10, 10-20, 20-30, 30-40, 40-50, 50-60, 60-70, 70-80, 80-90, or 90-99.
  • the multisubunit nucleic acid is a DNA or an RNA.
  • the RNA is an mRNA.
  • the mRNA is obtained or synthesized through a single IVT process or step.
  • the linker sequence encodes a linker peptide.
  • the linker peptide is an amino acid linker, a zipper motif, a foldon, a scaffold, or a combination thereof.
  • the linker peptide is an amino acid linker.
  • the linker peptide is a zipper motif.
  • the linker peptide is a foldon.
  • the linker peptide is a scaffold.
  • the linker peptide comprises an amino acid linker and a zipper motif.
  • the linker peptide comprises an amino acid linker and a foldon.
  • the linker peptide comprises an amino acid linker and a scaffold. In some embodiments, the linker peptide comprises a zipper motif and a scaffold. In some embodiments, the linker peptide comprises a foldon and a scaffold. In some embodiments, the linker peptide comprises an amino acid linker, a zipper motif and a scaffold.
  • the amino acid linker comprises 2 to 49 amino acids. In some embodiments, the amino acid linker is a glycine serine linker, a glycine proline linker, a glycine threonine linker, an alanine serine linker, any combination of two amino acids, or a combination thereof.
  • the linker peptide has an amino acid sequence of any one of SEQ ID NOs: 12-51 or 19101-19105.
  • the self-assembling sequence encodes a self-assembling peptide.
  • the self-assembling peptide is lumazine synthase, MS2 coat protein, hepatitis B surface antigen (HBsAg) from Hepatitis B Virus, hepatitis B core antigen (HBcAg) from Hepatitis B virus, human papillomavirus LI (HPV LI) protein, matrix protein Ml from influenza A virus, ferritin, riboflavin synthase, dihydrolipoyl acetyltransferase (E2p), or a combination thereof, including their codon optimized nucleic acid sequences, fragments, mutants, variants, comparable equivalents or functional analogs thereof.
  • the ferritin comprises ferritin subunit or ferritin peptide.
  • the ferritin peptide is obtained or derived from Listeria innocua or Helicobacter pylori.
  • the ferritin peptide is obtained or derived from Listeria innocua ferritin or its fragment, mutant, variant, comparable equivalent, or functional analogs thereof.
  • the ferritin peptide is obtained or derived from Helicobacter pylori ferritin, or its fragment, mutant, variant, comparable equivalent, or functional analogs thereof.
  • the dihydrolipoyl acetyltransferase (E2p) is obtained or derived from Bacillus stearothermophilus, or its fragment, mutant, variant, comparable equivalent, or functional analogs thereof.
  • the lumazine synthase is obtained or derived from Aquifex species (for example, Aquifex aeolicus) or Bacillus species (for example, Bacillus subtilis), or its fragment, mutant, variant, comparable equivalent, or functional analogs thereof.
  • the MS2 coat protein is obtained or derived from Emesvirus zinderi, or its fragment, mutant, variant, comparable equivalent, or functional analogs thereof.
  • the self-assembling peptide has an amino acid sequence of any one of SEQ ID NOs: 1-11 or 19097-19100.
  • the cleavage sequence encodes a cleavage peptide. In some embodiments, the cleavage sequence encodes one or more cleavage peptides. In some embodiments, the cleavage peptide comprises one or more cleavage peptides, for example, cleavage peptide- 1, cleavage peptide-2, and so on. In some embodiments, the one or more cleavage peptides are optionally connected to each other by a linker peptide. In some embodiments, the cleavage peptide is a golgi specific cleavage peptide, self cleaving peptide, or a combination thereof.
  • the cleavage peptide has an amino acid sequence of any one of SEQ ID NOs: 52-66.
  • the signal sequence encodes a signal peptide.
  • the signal peptide is present on the amino-terminus of the first polypeptide.
  • the multisubunit nucleic acid further encodes a second signal peptide on the amino-terminus of all or some polypeptides.
  • the signal peptide has an amino acid sequence of any one of SEQ ID NOs: 67-86.
  • the target sequence encodes a target peptide.
  • the target peptide is encoded by a codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.
  • the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • the herpesvirus is selected from the group comprising herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella- zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), Kaposi’s sarcoma-associated herpesvirus (KSHV), or a combination thereof.
  • HSV1 herpes simplex virus 1
  • HSV2 herpes simplex virus 2
  • VZV varicella- zoster virus
  • CMV cytomegalovirus
  • HHV6 human herpesvirus 6
  • HHV7 human herpesvirus 7
  • EBV Epstein-Barr virus
  • KSHV Kaposi’s sarcoma-associated herpesvirus
  • the target peptide is a capsid protein of a herpesvirus, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.
  • the capsid protein has an amino acid sequence of any one of SEQ ID NOs: 87-772, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.
  • the target peptide is a tegument protein of a herpesvirus, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.
  • the tegument protein has an amino acid sequence of any one of SEQ ID NOs: 773-2566, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.
  • the target peptide is an envelope protein of a herpes simplex virus 1 (HSV1), wherein the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, glycoprotein C, glycoprotein D, glycoprotein I, glycoprotein E, or a combination thereof, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.
  • HSV1 herpes simplex virus 1
  • the target peptide is an envelope protein of a herpes simplex virus 2 (HSV2), wherein the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, glycoprotein C, glycoprotein D, glycoprotein I, glycoprotein E, or a combination thereof, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.
  • HSV2 herpes simplex virus 2
  • the target peptide is an envelope protein of a cytomegalovirus (CMV), wherein the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, glycoprotein 34 or gp34, glycoprotein 68 or gp68, UL131A, UL130, UL128, UL16, or a combination thereof, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.
  • CMV cytomegalovirus
  • the target peptide is an envelope protein of a Epstein-Barr virus (EBV), wherein the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, glycoprotein 350 or gp350, glycoprotein 220 or gp220, glycoprotein 42 or gp42, or a combination thereof, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.
  • EBV Epstein-Barr virus
  • the target peptide is an envelope protein of a varicella-zoster virus (VZV), wherein the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, or a combination thereof, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.
  • VZV varicella-zoster virus
  • the target peptide is an envelope protein of a human herpesvirus 6 (HHV6), wherein the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, or a combination thereof, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.
  • HHV6 human herpesvirus 6
  • the target peptide is an envelope protein of a human herpesvirus 7 (HHV7), wherein the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, or a combination thereof, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.
  • HHV7 human herpesvirus 7
  • the target peptide is an envelope protein of a Kaposi’s sarcoma-associated herpesvirus (KSHV), wherein the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, or a combination thereof, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.
  • KSHV Kaposi’s sarcoma-associated herpesvirus
  • the envelope protein has an amino acid sequence of any one of SEQ ID NOs: 2567-3557 or 15725-19096, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.
  • the target peptide is a regulatory protein of a herpesvirus, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.
  • the regulatory protein has an amino acid sequence of any one of SEQ ID NOs: 3558-4041, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.
  • the target peptide is a B cell epitope of a herpesvirus, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.
  • the B cell epitope has an amino acid sequence of any one of SEQ ID NOs: 4042-7752, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.
  • the target peptide is a T cell epitope of a herpesvirus, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.
  • the T cell epitope has an amino acid sequence of any one of SEQ ID NOs: 7753-15724, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.
  • the target peptide has an amino acid sequence of any one of SEQ ID NOs: 87-15724 or 15725-19096, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.
  • a lipid nanoparticle composition comprising a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and the multisubunit nucleic acid according to any of the preceding embodiments or paragraphs.
  • the cationic lipid comprises an ionizable lipid.
  • the cationic lipid is present in an amount from 10 mol percent to 70 mol percent.
  • the phospholipid is present in an amount from 2 mol percent to 65 mol percent.
  • the sterol is present in an amount from 20 mol percent to 65 mol percent.
  • the PEG-lipid is present in an amount from 0.2 mol percent to 2.0 mol percent.
  • the lipid nanoparticle composition additionally comprises an ionizable polymer.
  • the ionizable polymer is present in an amount from 1 mol percent to 25 mol percent.
  • the ionizable polymer is selected from the group comprising a chitosan, chitosan derivatives, cellulose derivatives, a poly-L-lysine (PLL), a protamine, a polyethyleneimine, and/or their derivatives or a combination thereof.
  • the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), or SM-102, or ALC-0315, or a combination thereof.
  • a vaccine comprising a lipid nanoparticle, wherein the lipid nanoparticle comprises a cationic lipid, a phospholipid, a sterol, a PEG- lipid, and the multisubunit nucleic acid according to any of the preceding embodiments or paragraphs.
  • the cationic lipid comprises an ionizable lipid.
  • the cationic lipid is present in an amount from 10 mol percent to 70 mol percent.
  • the phospholipid is present in an amount from 2 mol percent to 65 mol percent.
  • the sterol is present in an amount from 20 mol percent to 65 mol percent.
  • the PEG-lipid is present in an amount from 0.2 mol percent to 2.0 mol percent.
  • the lipid nanoparticle composition additionally comprises an ionizable polymer.
  • the ionizable polymer is present in an amount from 1 mol percent to 25 mol percent.
  • the ionizable polymer is selected from the group comprising a chitosan, chitosan derivatives, cellulose derivatives, a poly-L-lysine (PLL), a protamine, a polyethyleneimine, and/or their derivatives or a combination thereof.
  • the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), or formula (VIII), or SM-102, or ALC-0315, or a combination thereof.
  • provided herein is a method of treating or preventing a disease, comprising administering to a subject in need thereof the multisubunit nucleic acid disclosed herein.
  • provided herein is a method of treating or preventing a disease, comprising administering to a subject in need thereof the multisubunit peptide disclosed herein.
  • lipid nanoparticle composition disclosed herein.
  • provided herein is a method of treating or preventing a disease, comprising administering to a subject in need thereof, the vaccine comprising the multisubunit nucleic acid disclosed herein.
  • provided herein is a method of treating or preventing a disease, comprising administering to a subject in need thereof, the vaccine comprising the multisubunit peptide disclosed herein.
  • provided herein is a method of treating or preventing a disease, comprising administering to a subject in need thereof, the vaccine comprising the lipid nanoparticle or lipid nanoparticle composition disclosed herein.
  • provided herein is use of the multisubunit nucleic acid disclosed herein, in the manufacture of a medicament for the treatment or prevention of a disease in a subject.
  • provided herein is use of the vaccine comprising the multisubunit nucleic acid disclosed herein, in the manufacture of a medicament for the treatment or prevention of a disease in a subject.
  • lipid nanoparticle composition disclosed herein, in the manufacture of a medicament for the treatment or prevention of a disease in a subject.
  • provided herein is use of the vaccine comprising the lipid nanoparticle or lipid nanoparticle composition disclosed herein, in the manufacture of a medicament for the treatment or prevention of a disease in a subject.
  • a multisubunit peptide comprising two or more polypeptides, wherein some or all polypeptides comprises either a target peptide, a linker peptide, and a self-assembling peptide, or a linker peptide, a target peptide, a linker peptide, and a self-assembling peptide, or a combination thereof, wherein one polypeptide is connected to another polypeptide by a cleavage peptide, wherein the multisubunit peptide includes a signal peptide upstream (amino-terminus) of one or more of the polypeptides, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • the signal peptide is present on the amino-terminus of the first polypeptide.
  • the signal peptide is
  • polypeptide nanoparticle comprising at least 2 or up to 500 polypeptides disclosed herein.
  • the polypeptides are homologous polypeptides, heterologous polypeptides, oligomeric complexes, polypeptide clusters, or a combination thereof.
  • the polypeptide nanoparticle is icosahedral, helical, spherical, rod-like, or a combination thereof.
  • a multisubunit nucleic acid sequence comprising two or more polynucleotide sequences, wherein some or all polynucleotide sequences comprises either a target sequence, a linker sequence, and a self-assembling sequence, or a linker sequence, a target sequence, a linker sequence, and a self-assembling sequence, or a combination thereof, wherein one polynucleotide sequence is connected to another polynucleotide sequence by a cleavage sequence, wherein the multisubunit nucleic acid sequence includes a signal sequence upstream of one or more of the polynucleotide sequences, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • the linker sequence connects the signal sequence with the first polynucleotide sequence. In some embodiments, the signal sequence is present upstream of all or some of the polynucleotide sequences. In some embodiments, the signal sequence is present upstream of the first polynucleotide sequence. In some embodiments, the signal sequence is present upstream of all polynucleotide sequences. In some embodiments, the linker sequence connects the target sequence with the self-assembling sequence in a polynucleotide sequence. In some embodiments, one linker sequence connects the cleavage sequence with the target sequence and another linker sequence connects the target sequence with the self-assembling sequence in a polynucleotide sequence.
  • the multisubunit nucleic acid sequence is a DNA or an RNA. In some embodiments, the multisubunit nucleic acid sequence is an mRNA. In some embodiments, the multisubunit nucleic acid sequence encodes a multisubunit peptide. In some embodiments, the multisubunit nucleic acid sequence is encapsulated or formulated in a lipid nanoparticle composition. In some embodiments, the multisubunit nucleic acid sequence is obtained or synthesized through one or more in vitro transcription (IVT) process. In some embodiments, the multisubunit nucleic acid sequence (for example, mRNA) is obtained or synthesized through a single in vitro transcription (IVT) process or step.
  • IVT in vitro transcription
  • the multisubunit nucleic acid sequence for example, mRNA
  • IVT single in vitro transcription
  • the disclosure relates to a multisubunit nucleic acid sequence encoding a multisubunit peptide described herein.
  • the disclosure relates to a vaccine comprising a multisubunit nucleic acid sequence encoding a multisubunit peptide described herein.
  • the disclosure relates to a multisubunit nucleic acid sequence encoding a multisubunit peptide comprising two or more polypeptides, wherein some or all polypeptides comprises either a target peptide, a linker peptide, and a selfassembling peptide, or a linker peptide, a target peptide, a linker peptide, and a selfassembling peptide, or a combination thereof, wherein one polypeptide is connected to another polypeptide by a cleavage peptide, wherein the multisubunit peptide includes a signal peptide upstream of one or more of the polypeptides, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • a signal peptide is present upstream (amino-terminus) of all or some of the polypeptides. In some embodiments, a signal peptide is present upstream (amino-terminus) of the first polypeptide. In some embodiments, a signal peptide is present upstream (amino-terminus) of all polypeptides.
  • the disclosure relates to a vaccine comprising a multisubunit nucleic acid sequence encoding a multisubunit peptide, wherein the multisubunit peptide comprises two or more polypeptides, wherein some or all polypeptides comprises either a target peptide, a linker peptide, and a self-assembling peptide, or a linker peptide, a target peptide, a linker peptide, and a self-assembling peptide, or a combination thereof, wherein one polypeptide is connected to another polypeptide by a cleavage peptide, wherein the multisubunit peptide includes a signal peptide upstream (amino-terminus) of one or more of the polypeptides, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • signal peptide is present upstream (amino-terminus) of all or some of the polypeptides. In some embodiments, signal peptide is present upstream (amino-terminus) of the first polypeptide. In some embodiments, signal peptide is present upstream (amino-terminus) of all the polypeptides.
  • the disclosure also relates to a multisubunit peptide comprising two or more polypeptides, wherein some or all polypeptides comprises either a target peptide, a linker peptide, and a self-assembling peptide, or a linker peptide, a target peptide, a linker peptide, and a self-assembling peptide, or a combination thereof, wherein one polypeptide is connected to another polypeptide by a cleavage peptide, wherein the multisubunit peptide includes a signal peptide upstream (amino-terminus) of one or more of the polypeptides, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • signal peptide is present upstream (amino-terminus) of all or some of the polypeptides. In some embodiments, signal peptide is present upstream (amino-terminus) of the first polypeptide. In some embodiments, signal peptide is present upstream (amino-terminus) of all the polypeptides.
  • the disclosure also relates to a vaccine comprising a multisubunit peptide, wherein the multisubunit peptide comprises two or more polypeptides, wherein some or all polypeptides comprises either a target peptide, a linker peptide, and a self-assembling peptide, or a linker peptide, a target peptide, a linker peptide, and a self-assembling peptide, or a combination thereof, wherein one polypeptide is connected to another polypeptide by a cleavage peptide, wherein the multisubunit peptide includes a signal peptide upstream (amino-terminus) of one or more of the polypeptides, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • a signal peptide is present upstream (amino-terminus) of all or some of the polypeptides. In some embodiments, a signal peptide is present upstream (amino-terminus) of the first polypeptide. In some embodiments, a signal peptide is present upstream (amino-terminus) of all the polypeptides.
  • the linker peptide connects the signal peptide with the first polypeptide in a multisubunit peptide. In some embodiments, the linker peptide connects the target peptide with the self-assembling peptide in a polypeptide. In some embodiments, one linker peptide connects the cleavage peptide with the target peptide and another linker peptide connects the target peptide with the self-assembling peptide in a polypeptide.
  • the multisubunit peptide comprises homologous polypeptides. In some embodiments, the multisubunit peptide comprises heterologous polypeptides. In some embodiments, the multisubunit peptide comprises homologous polypeptides, or heterologous polypeptides. In some embodiments, the disclosure relates to a polypeptide nanoparticle comprising one or more homologous polypeptides, one or more heterologous polypeptides, one or more oligomeric complexes, one or more polypeptide clusters, or a combination thereof.
  • the homologous polypeptides, heterologous polypeptides, oligomeric complexes, or polypeptide clusters comprise either a target peptide, a linker peptide, and a self-assembling peptide, or a linker peptide, a target peptide, a linker peptide, and a self-assembling peptide, or a combination thereof, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • the polypeptides in a polypeptide nanoparticle may also have some residues (amino acids) of the cleavage peptide.
  • the disclosure relates to a polypeptide nanoparticle formed from the self-assembly of two or more polypeptides, wherein some or all polypeptides comprises either a target peptide, a linker peptide, and a self-assembling peptide, or a linker peptide, a target peptide, a linker peptide, and a self-assembling peptide or a combination thereof, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • the polypeptides in the polypeptide nanoparticle may also have some residues (amino acids) of the cleavage peptide.
  • the polypeptide nanoparticle comprises of homologous polypeptides, heterologous polypeptides, oligomeric complexes, polypeptide clusters, or combination thereof.
  • provided herein is the multisubunit nucleic acid sequence described herein, encapsulated or formulated in a lipid nanoparticle composition.
  • the lipid nanoparticle composition comprises a cationic lipid, a phospholipid, a sterol, a PEG lipid and the multisubunit nucleic acid sequence described herein.
  • the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), or a combination thereof.
  • a vaccine comprising the multisubunit nucleic acid sequences described herein, encapsulated or formulated in a lipid nanoparticle composition.
  • the lipid nanoparticle composition comprises a cationic lipid, a phospholipid, a sterol, a PEG lipid and the multisubunit nucleic acid sequence described herein.
  • the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), or a combination thereof.
  • the lipid nanoparticle composition comprising an ionizable polymer, a cationic lipid, a phospholipid, a sterol, a PEG-lipid and the multisubunit nucleic acid sequence described herein.
  • the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula
  • provided herein is a method of treating or preventing a disease, comprising administering to a subject in need thereof the multisubunit nucleic acid sequence as described herein.
  • provided herein is a method of treating or preventing a disease, comprising administering to a subject in need thereof a vaccine comprising the multisubunit nucleic acid sequence as described herein.
  • a method of treating or preventing a disease comprising administering to a subject in need thereof a lipid nanoparticle composition comprising a cationic lipid, a phospholipid, a sterol, a PEG-lipid and the multisubunit nucleic acid sequence as described herein.
  • the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula (IV), formula
  • a method of treating or preventing a disease comprising administering to a subject in need thereof a lipid nanoparticle composition comprising an ionizable polymer, a cationic lipid, a phospholipid, a sterol, a PEG-lipid and the multisubunit nucleic acid sequence as described herein.
  • the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula
  • the disclosure relates to use of a lipid nanoparticle composition comprising a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and the multisubunit nucleic acid sequence as described herein, in the manufacture of a medicament for the treatment or prevention of a disease in a subject.
  • the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula (IV), formula
  • the self-assembling sequence encodes a self-assembling peptide.
  • the self-assembling peptide includes, but not limited to, lumazine synthase, MS2 coat protein, hepatitis B surface antigen (HBsAg) from Hepatitis B Virus, hepatitis B core antigen (HBcAg) from hepatitis B virus, human papillomavirus LI (HPV LI) protein, matrix protein Ml from influenza A virus, ferritin, riboflavin synthase, dihydrolipoyl acetyltransferase (E2p), or a combination thereof, including their fragments, mutants, variants, comparable equivalents, or functional analogs thereof.
  • ferritin comprises ferritin subunit or ferritin peptide.
  • the ferritin peptide is obtained or derived from Listeria innocua or Helicobacter pylori.
  • the ferritin peptide is a Listeria innocua ferritin or its fragment, mutant, variant, comparable equivalent, or functional analogs thereof.
  • the ferritin peptide is a Helicobacter pylori ferritin or its fragment, mutant, variant, comparable equivalent, or functional analogs thereof.
  • the cleavage sequence encodes a cleavage peptide.
  • the cleavage peptide comprises one or more cleavage peptides.
  • the cleavage peptide connects one polypeptide with another polypeptide, for example, adjacent polypeptide.
  • the cleavage peptide carries a cleavage site.
  • the cleavage peptide carries one or more cleavage sites.
  • the cleavage peptide facilitates the action of cellular proteases to cleave the multisubunit peptide into individual polypeptides.
  • the cleavage peptide self cleaves into individual polypeptides.
  • the cleavage peptide comprises two or more cleavage peptides (for example, cleavage peptide- 1, cleavage peptide-2 and so on), optionally connected via a linker.
  • the cleavage peptide self cleaves into individual polypeptides or is cleaved by the action of cellular proteases.
  • the cleavage peptide is a substrate for cellular proteases.
  • the cleavage peptide is a substrate for golgi specific proteases.
  • the cleavage peptide is a self cleaving peptide.
  • the cleavage peptide comprises two or more cleavage peptides (for example, cleavage peptide - 1, cleavage peptide-2 and so on), optionally linked by a linker peptide, wherein one cleavage peptide is a substrate for cellular proteases and the other cleavage peptide is a self cleaving peptide.
  • the signal sequence encodes a signal peptide.
  • the signal peptide is present upstream (amino-terminus) of one or more polypeptides in a multisubunit peptide. In some embodiments, the signal peptide is present upstream (amino-terminus) of the first polypeptide. In some embodiments, the signal peptide is present upstream (amino-terminus) of some polypeptides. In some embodiments, the signal peptide is present upstream (amino-terminus) of all polypeptides. In some embodiments, the signal peptide transports the multisubunit peptide to cell organelles. In some embodiments, the signal peptide transports the multisubunit peptide to golgi body or golgi apparatus. In some embodiments, the signal peptide is a golgi targeting signal peptide.
  • the present disclosure also includes a method of transforming a cell with the multisubunit nucleic acid sequence as described herein.
  • FIG. 1 - shows representative schematic illustration of multisubunit nucleic acid sequence wherein each polynucleotide sequence (PS) comprises a target sequence (TS), a linker sequence (LS), and a self-assembling sequence (SAS) or a linker sequence (LS), a target sequence (TS), a linker sequence (LS), and a self-assembling sequence (SAS), wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • PS polynucleotide sequence
  • LS linker sequence
  • SAS self-assembling sequence
  • the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • the multisubunit nucleic acid sequence has a signal sequence (SS) upstream of the first polynucleotide sequence.
  • SS signal sequence
  • the letter ‘n’ in figure 1 represents any number between 1 to 98.
  • the multisubunit nucleic acid sequence may additionally have 5’ cap and 3’ poly(A) tail. This multisubunit nucleic acid sequence encodes corresponding multisubunit peptide depicted in Figure 2.
  • FIG. 2 - shows representative schematic illustration of multisubunit peptide wherein each polypeptide (PP) comprises a target peptide (TP), a linker peptide (LP), and a self-assembling peptide (SAP) or a linker peptide (LP), a target peptide (TP), a linker peptide (LP), and a self-assembling peptide (SAP), wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • TP target peptide
  • LP linker peptide
  • SAP self-assembling peptide
  • cleavage peptide CP
  • SP signal peptide
  • the present disclosure relates to multisubunit nucleic acid sequences, multisubunit peptides, polypeptide nanoparticle, and their compositions for vaccine and therapeutic purpose against herpesviruses.
  • the lipid nanoparticle comprises one or more lipid components, an ionizable polymer component, and a multisubunit nucleic acid.
  • the cationic lipid is represented by any one of formulas (I), formulas (II), formulas (III), formulas (IV), formulas (V), formulas (VI), formulas (VII), formulas (VIII), or a combination thereof.
  • the multisubunit nucleic acid associated with the lipid nanoparticle is a DNA, an mRNA, a micro RNA, a small interfering RNA, a small nucleolar RNA, a small nuclear RNA, a long non-coding RNA or a combination thereof.
  • the lipid nanoparticle composition contains one or more pharmaceutical carriers or excipients, such as but not limited to, buffering agents, stabilizers, tonicity modifiers, surfactants, chelating agents, salts, anti-oxidants, diluents, and/or preservatives or a combination thereof.
  • the term lipid nanoparticle also denotes lipid nanoparticles that are devoid of any encapsulated multisubunit nucleic acid (empty lipid nanoparticles or ghost lipid nanoparticles).
  • the lipid nanoparticle composition comprises lipid nanoparticles with encapsulated multisubunit nucleic acid as well as empty lipid nanoparticles.
  • preventing is art-recognized, and when used in relation to a condition, such as an infection is well understood in the art, and includes administration of a composition, which reduces the frequency or severity, or delays the onset, of one or more symptoms of the medical condition in a subject relative to a subject who does not receive the composition.
  • the prevention of a condition, such as an infection includes, for example, the reduction of the frequency or severity of one or more symptoms of the medical condition in a population of patients receiving a therapy relative to a control population that did not receive the therapy, e.g., by a statistically and/or clinically significant amount.
  • the prevention of an infection includes reducing the likelihood that a patient receiving a therapy will develop the infection or related symptoms, relative to a patient who does not receive the therapy.
  • molar percent has been used interchangeably to mean number of moles of a component expressed as percentage relative to total moles of all lipid components present in the lipid nanoparticle compositions described herein.
  • 50 mol % cationic lipid means, 50 mol % of cationic lipid is present in the lipid nanoparticle composition and other lipid components together constitute remaining 50 mol % such that the total amount of all the lipid components constitute 100 mol %.
  • mol % also denotes to mean number of moles of a component expressed as percentage relative to total moles of all lipid components (such as cationic lipid, phospholipid, sterol and PEG-lipid) and ionizable polymer component(s) present in the lipid nanoparticle composition described herein.
  • lipid components such as cationic lipid, phospholipid, sterol and PEG-lipid
  • 50 mol % of cationic lipid means, 50 mol % of cationic lipid is present in the lipid nanoparticle composition and other lipids components and ionizable polymer components together constitute the remaining 50 mol % such that the total amount of all the lipid components and ionizable polymer components constitute 100 mol %.
  • N/P ratio means the ratio (molar ratio) of the positive charges in the cationic lipid relative to the negative charges in the nucleic acid (such as the multisubunit nucleic acid sequence disclosed herein) in a lipid nanoparticle.
  • the N/P ratio refers to the ratio of protonable nitrogen present in the cationic lipid relative to the phosphate present in the nucleic acid in a lipid nanoparticle.
  • the N/P ratio is between 1 to 18 (i.e., 1 :1 to 18:1).
  • a N/P ratio of 18 refers to the presence of 18 protonable nitrogen of the cationic lipid relative to 1 phosphate of the nucleic acid in a lipid nanoparticle.
  • antibody and “antibodies” have been used interchangeably herein and means any antibody or antibody fragment (whether produced naturally or recombinantly) which retains antigen binding activity. This includes a monoclonal or polyclonal antibody, a single chain antibody, a Fab fragment of a monoclonal or polyclonal antibody, a chimeric antibody, a humanized antibody, a human antibody, a bispecific antibody, a multispecific antibody, or a nanobody.
  • cell as used herein means a single cell or a population of cells or plurality of cells.
  • biologically effective amount or “therapeutically effective amount” as used herein means an amount of an agent, for example, a therapeutic, drug, therapeutic agent, prophylactic agent, diagnostic agent, composition, etc., that is sufficient, when administered to a subject suffering from or susceptible to an infection, disease, disorder, and/or condition, to treat, prevent, diagnose, improve symptoms of, and/or delay the onset of the infection, disease, disorder, and/or condition.
  • a therapeutically effective amount herein may vary according to factors such as the disease state, age, sex, and weight of the patient.
  • mammals include, but are not limited to, any member of the mammalian class: humans, non-human primates such as chimpanzees, and other apes and monkey species; farm animals such as cattle, horses, sheep, goats, swine; domestic animals such as rabbits, dogs, and cats; laboratory animals including rodents, such as rats, mice, ferrets, and guinea pigs, and the like.
  • the term does not denote a particular age or gender.
  • an individual “at risk” of developing a particular disease, disorder, or condition may or may not have detectable disease or symptoms of disease, and may or may not have displayed detectable disease or symptoms of disease prior to the treatment methods described herein.
  • “At risk” denotes that an individual has one or more risk factors, which are measurable parameters that correlate with development of a particular disease, disorder, or condition, as known in the art. An individual having one or more of these risk factors has a higher probability of developing a particular disease, disorder, or condition than an individual without one or more of these risk factors.
  • the term “vaccine” as used herein means a substance or composition comprising an antigen or immunogen for eliciting an immune response in a subject against the antigen or the immunogen.
  • the term vaccine is also understood to mean a substance or composition comprising an antigen or immunogen that activates or stimulates an immune cell.
  • the antigen or immunogen is a peptide, a protein, a polysaccharide, or a combination thereof.
  • the antigen or immunogen is encoded by a nucleic acid, for example, a DNA, an RNA, or an mRNA.
  • the vaccine comprises a nucleic acid that encodes an antigen or an immunogen.
  • the vaccine comprises a multisubunit nucleic acid as described herein.
  • the signal sequence is present upstream of the first polynucleotide sequence. In some embodiments, the signal sequence is present upstream of some polynucleotide sequences. In some embodiments, the signal sequence is present upstream of each of the polynucleotide sequences. In some embodiments, the polynucleotide sequence comprises a target sequence, a linker sequence, and a self-assembling sequence, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • the linker sequence connects the signal sequence with the first polynucleotide sequence.
  • the signal sequence is present upstream of each of some or all of the polynucleotide sequences.
  • the multisubunit nucleic acid sequence is obtained or synthesized through a single in vitro transcription (IVT) process or step. The multisubunit nucleic acid sequence encodes multisubunit peptide.
  • the signal peptide is present on the amino-terminus of the first polypeptide. In some embodiments, the signal peptide is present on the amino-terminus of some polypeptides. In some embodiments, the signal peptide is present on the aminoterminus of each of the polypeptides. In some embodiments, the polypeptide comprises a target peptide, a linker peptide, and a self- assembling peptide, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • the multisubunit peptide either comprises a target peptide, a linker peptide, and a self- assembling peptide, or a linker peptide, a target peptide, a linker peptide, and a self-assembling peptide, or a combination thereof, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus, such that the total number of polypeptides in a multisubunit peptide are not more than 100.
  • the linker peptide connects the signal peptide with the polypeptide.
  • the signal peptide is present on the amino-terminus of each of some or all polypeptides.
  • the multisubunit peptide may comprise homologous polypeptides or heterologous polypeptides.
  • polynucleotide sequence as used herein means a sequence of nucleotides that encodes a polypeptide.
  • protein or “peptide” have been used interchangeably herein and mean a polymer of amino acids linked through peptide bonds, but do not imply any specific length.
  • the term also includes fusion proteins, muteins, analogs or modified forms.
  • polypeptide as used herein means a sequence of amino acids that comprises either a target peptide, a linker peptide, and a self-assembling peptide or a linker peptide, a target peptide, a linker peptide, and a self-assembling peptide, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • the polypeptide comprises a target peptide, a linker peptide, and a self-assembling peptide, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • the polypeptide comprises a linker peptide, a target peptide, a linker peptide, and a self-assembling peptide, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • the polypeptide may have some residues (amino acids) of cleavage peptide.
  • the polypeptide comprises a signal peptide.
  • target sequence means a sequence of nucleotides that encodes a target peptide obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • target peptide as used herein means a sequence of amino acids obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • the target peptides in two or more polypeptides are identical i.e., homologous polypeptides.
  • the target peptides in two or more polypeptides are different i.e., heterologous polypeptides.
  • signal sequence as used herein means a sequence of nucleotides that encodes a signal peptide.
  • the signal peptide is present on the N-terminus of all polypeptides. In some embodiments, the signal peptide is encoded by signal sequence. In some embodiments, the signal peptide is a golgi targeting signal peptide.
  • cleavage peptide as used herein means a sequence of amino acids that facilitates the action of cellular proteases to cleave the multisubunit peptide into individual polypeptides or self cleaves into individual polypeptides.
  • the cleavage peptide is present between any two polypeptides. It connects one polypeptide with another polypeptide, for example, adjacent polypeptide.
  • the cleavage peptide carries one or more cleavage sites.
  • the cleavage peptide is a substrate for proteases.
  • cleavage peptide undergoes self cleavage to result in individual polypeptides.
  • the cleavage peptide is a substrate for golgi specific proteases.
  • the cleavage peptide comprises one or more cleavage peptides, for example, cleavage peptide- 1, cleavage peptide-2 and so on.
  • the cleavage peptide optionally comprises a linker peptide between two cleavage peptides.
  • the cleavage peptide self cleaves into individual polypeptides or is cleaved by the action of cellular proteases.
  • the cleavage peptide is a substrate for cellular proteases.
  • the cleavage peptide is a substrate for golgi specific proteases. In some embodiments, the cleavage peptide is a self cleaving peptide. In some embodiments, the cleavage peptide comprises two or more cleavage peptides (for example, cleavage peptide- 1, cleavage peptide-2 and so on), optionally linked by a linker peptide, wherein one cleavage peptide is a substrate for cellular proteases and the other cleavage peptide is a self cleaving peptide.
  • linker sequence as used herein means a sequence of nucleotides that encodes a linker peptide.
  • linker peptide or “peptide linker” have been used interchangeably to mean a sequence of amino acids that either connects the target peptide with the selfassembling peptide, connects the signal peptide with the target peptide, connects the cleavage peptide with the target peptide, connects the signal peptide with the polypeptide, or connects two cleavage peptides.
  • the linker peptide connects the signal peptide with the polypeptide.
  • the linker peptide connects the target peptide with the self-assembling peptide in a polypeptide.
  • one linker peptide connects the cleavage peptide with the target peptide and another linker peptide connects the target peptide with the self-assembling peptide in a polypeptide. In some embodiments, one linker peptide connects the cleavage peptide with the target peptide and another linker peptide connects the target peptide with the self-assembling peptide. In some embodiments, one linker peptide connects cleavage peptide with the target peptide and another linker peptide connects the signal peptide with the target peptide. In some embodiments, the linker peptide connects two cleavage peptides.
  • the linker peptide is an amino acid linker, a zipper motif, a foldon, a scaffold, or a combination thereof. In some embodiments, the linker peptide is an amino acid linker. In some embodiments, the linker peptide is a foldon. In some embodiments, the linker peptide is a zipper motif. In some embodiments, the linker peptide is a scaffold. In some embodiments, the linker peptide comprises an amino acid linker and a zipper motif. In some embodiments, the linker peptide comprises an amino acid linker and a foldon. In some embodiments, the linker peptide comprises an amino acid linker and a scaffold.
  • the linker peptide comprises a zipper motif and a scaffold. In some embodiments, the linker peptide comprises a foldon and a scaffold. In some embodiments, the linker peptide comprises an amino acid linker, a zipper motif, and a scaffold. In some embodiments, the linker peptide comprises an amino acid linker, a foldon, and a scaffold.
  • amino acid linker sequence means a sequence of nucleotides that encodes an amino acid linker.
  • amino acid linker means a sequence of amino acids that provides structural integrity to polypeptide such that the components of the polypeptide remain, as far as possible, in their native or stable conformation.
  • amino acid linker also helps in orientation of a polypeptide such that the domains or epitopes on the target peptide are exposed or displayed for interaction or communication with cells or biomolecules or immune system in the absence of foldon or scaffold.
  • the amino acid linker connects two cleavage peptides.
  • amino acid linkers includes, glycine serine linker, glycine proline linker, glycine threonine linker, alanine serine linker, any combination of two amino acids or a combination thereof. In some embodiments, amino acid linker is about 2-49 amino acid long.
  • glycine serine linker sequence as used herein means a sequence of nucleotides that encodes a glycine serine linker.
  • glycine serine linker as used herein means a sequence of amino acid comprising one or more glycine (G) and serine (S) in any combinations without any preference of order or limitation on number of appearances of either glycine or serine.
  • G glycine
  • S serine
  • the glycine serine linker is few amino acids in length to several amino acids in length.
  • zipper sequence as used herein means a sequence of nucleotides that encodes a zipper motif.
  • zipper motif or “zipper peptide” as used herein means a sequence of amino acids that facilitates homologous polypeptides or heterologous polypeptides to come together or associate to form a polypeptide cluster.
  • foldon sequence means a sequence of nucleotides that encodes a foldon.
  • foldon means a sequence of amino acids that enables two or more homologous polypeptides to organise to form an oligomeric complex. In some embodiments, the foldon also helps in orientation of a polypeptide such that the domains or epitopes on the target peptide are exposed or displayed for interaction or communication with cells or biomolecules or immune system.
  • scaffold sequence as used herein means a sequence of nucleotides that encodes a scaffold.
  • scaffold as used herein means a sequence of amino acids that provides structural and/or functional integrity or support to the target peptide and helps in orientation of target peptide such that the domains or epitopes of the target peptide are exposed or displayed for interaction or communication with cells or biomolecules or immune system.
  • oligomeric complex means a complex formed by two or more homologous polypeptides.
  • the oligomeric complex has at least two homologous polypeptides, at least three homologous polypeptides, at least four homologous polypeptides, at least five homologous polypeptides, or at least six homologous polypeptides and so on.
  • polypeptide cluster as used herein means a complex formed by interaction of protein domains of two or more homologous polypeptides or two or more heterologous polypeptides orchestrated by the zipper motif. In some embodiments, the polypeptide cluster has at least two, at least three, at least four, at least five, at least six homologous polypeptides, heterologous polypeptides, or combination thereof.
  • self- assembling sequence means a sequence of nucleotides that encodes a self-assembling peptide.
  • self-assembling peptide means a sequence of amino acids that enables the polypeptides to self-assemble into a polypeptide nanoparticle.
  • the term “self-assembly” or “self-assemble” or “self-assembling” has been used interchangeably to means the ability of polypeptides to undergo multimerization to form a polypeptide nanoparticle.
  • the polypeptide nanoparticle has at least two polypeptides (dimer or 2-mer), at least three polypeptides (trimer or 3-mer), at least four polypeptides (tetramer or 4-mer), at least five polypeptides (pentamer or 5-mer), at least six polypeptides (hexamer or 6-mer), at least seven polypeptides (heptamer or 7-mer), at least eight polypeptides (octamer or 8-mer), and so on.
  • the polypeptide nanoparticle is up to 500-mers.
  • hydrogen bonds, disulfide bonds, hydrophobic interactions, electrostatic interactions, and/or Van der Waals forces combine to maintain self-assembled structure.
  • multimerization means association of two or more units of homologous polypeptides, heterologous polypeptides, oligomeric complexes, polypeptide clusters, or their combination.
  • polypeptide nanoparticle as used herein means a nanoparticle formed by self-assembly of polypeptides.
  • the polypeptide nanoparticle comprises two or more homologous polypeptides, two or more heterologous polypeptides, one or more oligomeric complexes, one or more polypeptide clusters, or a combination thereof.
  • homologous polypeptides as used herein means polypeptides in a multisubunit peptide that have identical target peptides. For example, if two polypeptides in the multisubunit peptide have identical target peptides they are considered to be homologous polypeptides.
  • heterologous polypeptide as used herein means polypeptides in a multisubunit peptide that have different target peptides. For example, if two polypeptides in the multisubunit peptide have different or non-identical target peptides, they are considered to be heterologous polypeptides.
  • upstream has been used interchangeably in the context of amino acid sequences (protein, peptide, polypeptide, or any other sequence composed of amino acids) or the nucleic acid sequences (DNA, RNA or any other sequence composed of nucleotides) to mean amino end of an amino acid sequence or the 5-prime end of a nucleic acid sequence respectively.
  • fragment as used herein, whether in the context of a nucleic acid, nucleotide, protein, polypeptide, or peptide, means any length of the nucleic acid, protein, polypeptide, or peptide sequence except the full length of the respective nucleic acid, protein, polypeptide, or peptide sequence. Fragment includes such portions of nucleic acid, protein, polypeptide, or peptide that are capable of treating, preventing, diagnosing, improving symptoms of, and/or delay the onset of an infection, disease, disorder, and/or condition. A fragment is also understood to mean an immunogenic fragment of the protein, polypeptide or peptide, or a fragment of nucleic acid encoding an immunogenic fragment of the protein, peptide, or polypeptide.
  • variant as used herein, whether in the context of a nucleic acid, nucleotide, protein, polypeptide, or peptide sequence, means homologs, orthologs, paralogs, mutants or analogs of respective nucleic acid, protein, polypeptide, or peptide sequence.
  • mutant as used herein, whether in the context of a nucleic acid, nucleotide, protein, polypeptide, or peptide sequence, means a sequence which is not a wild type sequence. A mutant is also understood to mean a nucleic acid, nucleotide, protein, polypeptide, or peptide sequence that carries a mutation.
  • mutant as used herein means, a change or modification in the sequence of nucleic acid or amino acid in comparison to a reference sequence and includes insertion, deletion, substitution, or a combination thereof. Mutations are introduced to impart desirable properties upon the nucleic acid, nucleotide, protein, polypeptide, or peptide sequence. This includes, for example, enabling the nucleic acid, nucleotide, protein, polypeptide, or peptide sequence to elicit an immune response while ensuring that any undesirable or deleterious effects are minimized or entirely removed.
  • sequence means nucleic acid sequences, nucleic acids, polynucleotides, amino acid sequences, proteins, polypeptides, or peptides, depending upon the context in which the term sequence is used, to mean a sequence of nucleotides or amino acids.
  • sequence In the context of nucleic acid, polynucleotide, or nucleotide sequence, the sequence is represented by a single letter code representing the nitrogenous base, for example A, T, G, C, or U.
  • amino acid sequences, proteins, polypeptides, or peptides the sequence is represented by a single letter amino acid code as generally understood by persons skilled in the art.
  • the sequences representing target sequence or target peptide may contain a tag, for example, histidine tag, streptavidin tag etc, which may be deleted or removed from the respective sequence before employing the sequence in accordance with the present disclosure.
  • the sequences representing target sequence or target peptide may contain a signal sequence or signal peptide respectively, which may be deleted or removed from the respective sequence before employing the sequence in accordance with the present disclosure.
  • the deleted or removed signal sequence or signal peptide may be employed in accordance with the present disclosure.
  • the presence of tags, signal sequence or signal peptide, or other similar elements, may easily be recognized by those skilled in the art.
  • Percentage identity has been used interchangeably and means the extent of identity between two sequences (e.g. nucleic acid sequences or amino acid sequences). Percent identity can be determined by aligning two sequences, introducing gaps to maximize identity between the sequences. Percent identity should generally be calculated between the same types of sequences for example nucleic acids, i.e. for DNA sequences or RNA sequences or amino acid sequences. The alignment of sequences (nucleic acid or amino acid) can be performed with the appropriate pair wise sequence alignment programs. Identity can be calculated between two sequences by multiplying the number of matches in the pair by 100 and dividing by the length of the aligned region, including gaps.
  • the nucleic acid sequence or the amino acid sequence shares at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity with the sequences disclosed herein.
  • the nucleic acid sequence or the amino acid sequence shares at least 50% to 60%, at least 60% to 70%, at least 70% to 80%, at least 80% to 90%, or at least 90% to 100% identity with the sequences disclosed herein.
  • Suitable analog or “functional analogue” have been used interchangeably, whether in the context of nucleic acid sequence or amino acid (protein or peptide) sequence, and mean all sequences which essentially performs similar function compared to the sequence being referred.
  • functional analogs of a target peptide include all sequences, irrespective of their percentage identity, which essentially perform at least one function similar to the function the target peptide performs.
  • nucleic acid sequences amino acid sequences, proteins, polypeptides, or peptides, as disclosed herein, means structurally or functionally similar or identical nucleic acid sequences, amino acid sequences, proteins, polypeptides, or peptides compared to the nucleic acid sequences or amino acid sequences being referred.
  • envelope protein as used herein means a protein associated with the viral envelope, for example, anchored into, projecting from, or across the lipid layer of the viral envelope. Envelope proteins mediate attachment and fusion. In some embodiments, envelope proteins are glycosylated.
  • capsid protein or “nucleocapsid protein” as used herein means a protein that encapsidates or packages the viral genetic material or genome.
  • the term is also understood to mean those proteins which are involved or participate in one or more of the following functions or activities, such as virus assembly, budding or release of virus, mediating attachment to and penetration into the host cells (especially in case of non- enveloped viruses), packaging the genome, etc.
  • the capsid protein or nucleocapsid proteins are the proteins associated with viral capsid or viral nucleocapsid or viral core.
  • matrix protein as used herein means a protein that is found beneath the viral envelope, often acting as a bridge between nucleocapsid or core and the envelope.
  • structural protein means proteins that are components of the viral particle or structure, for example, capsid proteins, membrane or envelope proteins, proteins packaged within the virus particle etc.
  • non-structural protein means proteins that are encoded by the virus, but are not the component or part of the mature viral particle or structure, for example, enzymes, transcription factors etc.
  • B cell epitope as used herein means a protein determinant that is recognized by B cell receptors (BCR) and capable of specific binding to an antibody or immunoglobulin.
  • T cell epitope as used herein means a protein determinant derived from an antigen which is presented by an antigen presenting cell (APC) through major histocompatibility complex (MHC) for recognition by a T cell receptor (TCR).
  • APC antigen presenting cell
  • MHC major histocompatibility complex
  • herpesvirus “human herpesvirus”, “HSV”, or “HHSV” have been used interchangeably and mean herpesviruses belonging to the family herpesviridae, including but not limited to, herpes simplex virus 1 or human herpesvirus 1 (HSV1 or HHV1), herpes simplex virus 2 or human herpesvirus 2 (HSV2 or HHV2), varicella-zoster virus or human herpesvirus 3 (VZV or HHV3), Epstein-Barr virus or human herpesvirus 4 (EBV or HHV4), cytomegalovirus or human herpesvirus 5 (CMV or HHV5), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), and Kaposi’s sarcoma-associated herpesvirus or human herpesvirus 8 (KSHV or HHV8).
  • HSV1 or HHV1 herpes simplex virus 1
  • HSV2 or HHV2 herpes simple
  • herpes simplex virus 1 has been used interchangeably to refer to herpes simplex virus 1 belonging to the subfamily Alphaherpesvirinae.
  • herpes simplex virus 2 has been used interchangeably to refer to herpes simplex virus 2 belonging to the subfamily Alphaherpesvirinae.
  • variable cella-zoster virus has been used interchangeably to refer to varicella-zoster virus belonging to the subfamily Alphaherpesvirinae.
  • Epstein-Barr virus has been used interchangeably to refer to Epstein-Barr virus belonging to the subfamily Gammaherpesvirinae.
  • cytomegalovirus human herpesvirus 5
  • CMV human herpesvirus 5
  • HHV5 cytomegalovirus belonging to the subfamily Betaherpesvirinae.
  • human herpesvirus 6 or “HHV6” has been used interchangeably to refer to human herpesvirus 6 belonging to the subfamily Betaherpesvirinae.
  • the multisubunit nucleic acid sequence is a DNA.
  • the DNA encodes a multisubunit peptide described herein.
  • Gammaherpesvirinae [Gamma (y) Herpesviruses] - which includes Epstein-Barr virus (EBV) and human herpesvirus 8 (HHV8) or Kaposi’s sarcoma-associated herpesvirus (KSHV).
  • EBV Epstein-Barr virus
  • HHV8 human herpesvirus 8
  • KSHV Kaposi’s sarcoma-associated herpesvirus
  • Exemplary major capsid protein includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 87-157, 158-164, 165-188, 189-254, 255-259, 260, 261-277, or 278-287 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma- associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • HSV1 herpes simplex virus 1
  • HSV2 herpes simplex virus 2
  • VZV varicella-zoster virus
  • CMV cytomegalovirus
  • HHV6 human her
  • the triplex monomer is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • the target peptide is obtained or derived from triplex dimer of a herpesvirus.
  • the triplex dimer is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • Exemplary triplex dimer includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 404-434, 435, 436-438, 439-445, 446-447, 448, 449- 453, or 454-466 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma- associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • HSV1 herpes simplex virus 1
  • HSV2 herpes simplex virus 2
  • VZV varicella-zoster virus
  • CMV cytomegalovirus
  • HHV6 human herpes
  • the triplex dimer is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • SCP Small capsid protein
  • the target peptide is obtained or derived from small capsid protein of a herpesvirus.
  • the small capsid protein is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • Exemplary small capsid protein includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 467-468, 469-470, 471-473, 474-478, 479- 480, 481, 482-494, or 495-501 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • HSV1 herpes
  • the small capsid protein shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the small capsid protein is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • the target peptide is obtained or derived from portal protein of a herpesvirus.
  • the portal protein is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • Exemplary portal protein includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 502-567, 568-574, 575-592, 593-646, 647-652, 653, 654-683, or 684-692 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma- associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the portal protein shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the portal protein is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • PCP Portal capping protein
  • the target peptide is obtained or derived from portal capping protein of a herpesvirus.
  • the portal capping protein is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • Exemplary portal capping protein includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 693-730, 731-734, 735-738, 739-742, 743- 747, 748, 749-762, or 763-772 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • HSV1 herpes simplex virus 1
  • HSV2 herpes simplex virus 2
  • VZV varicella-zoster virus
  • CMV cytomegalovirus
  • the portal capping protein shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the portal capping protein is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • the target peptide is obtained or derived from tegument protein of a herpesvirus.
  • the tegument protein is obtained or derived from herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), Kaposi’s sarcoma-associated herpesvirus (KSHV), or a combination thereof.
  • HSV1 herpes simplex virus 1
  • HSV2 herpes simplex virus 2
  • VZV varicella-zoster virus
  • CMV cytomegalovirus
  • HHV6 human herpesvirus 6
  • HHV7 human herpesvirus 7
  • EBV Epstein-Barr virus
  • KSHV Kaposi’s sarcoma-associated herpesvirus
  • the tegument protein is selected from the group comprising virion protein kinase, largest tegument protein, LTP binding protein, encapsidation and egress protein, cytoplasmic egress tegument protein, CETP binding protein, cytoplasmic egress facilitator- 1, encapsidation chaperone protein, capsid transport tegument protein, cytoplasmic egress facilitator-2, putative membrane or tegument protein, tegument protein pp65, tegument protein ppl50, pp85 protein, including mutants, derivatives, variants, comparable equivalents, or functional analogs, or a combination thereof of a herpesvirus.
  • Virion protein kinase VPK
  • the target peptide is obtained or derived from virion protein kinase of a herpesvirus.
  • the virion protein kinase is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • Exemplary virion protein kinase includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 773-794, 795-796, 797, 798, 799, or 800-806 of a herpesvirus, for example, herpes simplex virus 1 (HSV1), varicella-zoster virus (VZV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • HSV1 herpes simplex virus 1
  • VZV varicella-zoster virus
  • HHV6 human herpesvirus 6
  • HHV7 human herpesvirus 7
  • EBV Epstein-Barr virus
  • KSHV Kaposi’s sarcoma-associated her
  • the virion protein kinase shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the virion protein kinase is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • a target sequence which may be either a DNA, an RNA, or an mRNA.
  • the target peptide is obtained or derived from largest tegument protein of a herpesvirus.
  • the largest tegument protein is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • Exemplary largest tegument protein includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 807-941, 942-951, 952-1033, 1034-1265, 1266-1273, 1274, 1275-1453, or 1454-1475 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • HSV1 herpes simplex virus 1
  • HSV2 herpes simplex virus 2
  • VZV varicella-zoster virus
  • CMV cytomegalovirus
  • the largest tegument protein shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the largest tegument protein is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • LTP binding protein (LTPbp)
  • the target peptide is obtained or derived from LTP binding protein of a herpesvirus.
  • the LTP binding protein is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • Exemplary LTP binding protein includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 1476-1549, 1550-1555, 1556-1564, 1565- 1567, 1568-1572, 1573, 1574-1586, or 1587-1598 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • HSV1 herpes simplex virus 1
  • HSV2 herpes simplex virus 2
  • VZV varicella-zoster virus
  • CMV cytomegalovirus
  • the LTP binding protein shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the LTP binding protein is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • the target peptide is obtained or derived from encapsidation and egress protein of a herpesvirus.
  • the encapsidation and egress protein is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • Exemplary encapsidation and egress protein includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 1599-1633, 1634-1636, 1637- 1643, 1644, 1645-1647, 1648, 1649-1655, or 1656-1660 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • HSV1 herpes simplex virus 1
  • HSV2 herpes simplex virus 2
  • VZV varicella-zoster virus
  • CMV cytomegalo
  • the encapsidation and egress protein shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the encapsidation and egress protein is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • Cytoplasmic egress tegument protein (CETP)
  • the target peptide is obtained or derived from cytoplasmic egress tegument protein of a herpesvirus.
  • the cytoplasmic egress tegument protein is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • Exemplary cytoplasmic egress tegument protein includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 1661-1675, 1676, 1677-1678, 1679-1682, 1683-1686, 1687, 1688-1690, or 1691-1693 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • HSV1 herpes simplex virus 1
  • HSV2 herpes simplex virus 2
  • VZV varicella-zoster virus
  • CMV cytomegalo
  • the cytoplasmic egress tegument protein shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the cytoplasmic egress tegument protein is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • CETP binding protein CETPbp
  • the target peptide is obtained or derived from CETP binding protein of a herpesvirus.
  • the CETP binding protein is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • Exemplary CETP binding protein includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 1694-1729, 1730-1732, 1733-1738, 1739- 1741, 1742-1746, 1747, 1748-1751, or 1752-1760 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • HSV1 herpes simplex virus 1
  • HSV2 herpes simplex virus 2
  • VZV varicella-zoster virus
  • CMV cytomegalovirus
  • the CETP binding protein shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the CETP binding protein is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • Cytoplasmic egress facilitator-1 (CEF1)
  • the target peptide is obtained or derived from cytoplasmic egress facilitator- 1 of a herpesvirus.
  • Exemplary cytoplasmic egress facilitator- 1 includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 1761-1782, 1783, 1784-1789, 1790-1794, 1795-1799, 1800, 1801-1803, or 1804-1809 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • HSV1 herpes simplex virus 1
  • HSV2 herpes simplex virus 2
  • VZV varicella-zoster virus
  • CMV cytomegalovirus
  • the cytoplasmic egress facilitator- 1 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the cytoplasmic egress facilitator- 1 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • ECP Encapsidation chaperone protein
  • the target peptide is obtained or derived from encapsidation chaperone protein of a herpesvirus.
  • the encapsidation chaperone protein is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • Exemplary encapsidation chaperone protein includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 1810-1832, 1833-1834, 1835- 1839, 1840-1978, 1979-1981, 1982, 1983-1991, or 1992-1996 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • HSV1 herpes simplex virus 1
  • HSV2 herpes simplex virus 2
  • VZV varicella-zoster virus
  • CMV cytomegalovirus
  • the encapsidation chaperone protein shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the encapsidation chaperone protein is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • CTP Capsid transport tegument protein
  • the target peptide is obtained or derived from capsid transport tegument protein of a herpesvirus.
  • the capsid transport tegument protein is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • Exemplary capsid transport tegument protein includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 1997-2053, 2054-2058, 2059- 2069, 2070-2073, 2074-2078, 2079, 2080-2091, or 2092-2106 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • HSV1 herpes simplex virus 1
  • HSV2 herpes simplex virus 2
  • VZV varicella-zoster virus
  • CMV cytomegalovirus
  • the capsid transport tegument protein shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the capsid transport tegument protein is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • CEF2 Cytoplasmic egress facilitator-2
  • the target peptide is obtained or derived from cytoplasmic egress facilitator-2 of a herpesvirus.
  • the cytoplasmic egress facilitator-2 is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • Exemplary cytoplasmic egress facilitator-2 includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 2107-2147, 2148-2150, 2151- 2155, 2156-2195, 2196-2200, 2201, 2202-2210, or 2211-2221 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or
  • the cytoplasmic egress facilitator-2 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the cytoplasmic egress facilitator-2 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • the target peptide is obtained or derived from putative membrane or tegument protein of a herpesvirus.
  • the putative membrane or tegument protein is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • Exemplary putative membrane or tegument protein includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 2222-2238, 2239-2240, 2241- 2254, 2255-2258, 2259-2261, 2262, 2263-2265, or 2266-2271 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the putative membrane or tegument protein shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, fragment
  • the putative membrane or tegument protein is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • the target peptide is obtained or derived from tegument protein pp65 of a herpesvirus, for example, cytomegalovirus (CMV).
  • a herpesvirus for example, cytomegalovirus (CMV).
  • the tegument protein pp65 is a full length protein or a fragment thereof of a herpesvirus, for example, cytomegalovirus (CMV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • CMV cytomegalovirus
  • Exemplary tegument protein pp65 includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 2272-2314 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the tegument protein pp65 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the tegument protein pp65 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • the target peptide is obtained or derived from tegument protein ppl50 of a herpesvirus, for example, cytomegalovirus (CMV), human herpesvirus 6 (HHV6), or human herpesvirus 7 (HHV7).
  • a herpesvirus for example, cytomegalovirus (CMV), human herpesvirus 6 (HHV6), or human herpesvirus 7 (HHV7).
  • the tegument protein pp 150 is a full length protein or a fragment thereof of a herpesvirus, for example, cytomegalovirus (CMV), human herpesvirus 6 (HHV6), or human herpesvirus 7 (HHV7) comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • Exemplary tegument protein ppl50 includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 2315-2562, 2563-2564, or 2565 of a herpesvirus, for example, cytomegalovirus (CMV), human herpesvirus 6 (HHV6), or human herpesvirus 7 (HHV7), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • CMV cytomegalovirus
  • HHV6 human herpesvirus 6
  • HHV7 human herpesvirus 7
  • the tegument protein ppl50 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the tegument protein ppl50 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA. pp85 protein
  • the target peptide is obtained or derived from pp85 protein of a herpesvirus, for example, human herpesvirus 7 (HHV7).
  • a herpesvirus for example, human herpesvirus 7 (HHV7).
  • the pp85 protein is a full length protein or a fragment thereof of a herpesvirus, for example, human herpesvirus 7 (HHV7) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • HHV7 human herpesvirus 7
  • Exemplary pp85 protein includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NO: 2566 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the pp85 protein shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof. Given the amino acid sequences of the pp85 protein, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above pp85 protein. Such DNA or RNA sequences are deemed to be incorporated in this disclosure.
  • the pp85 protein is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • the target peptide is obtained or derived from envelope protein of a herpesvirus.
  • the envelope protein is obtained or derived from herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), Kaposi’s sarcoma-associated herpesvirus (KSHV), or a combination thereof
  • the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, glycoprotein C, glycoprotein D, glycoprotein I, or glycoprotein E, including mutants, derivatives, variants, comparable equivalents, or functional analogs, or a combination thereof of a herpes simplex virus 1 (HSV1).
  • the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, glycoprotein C, glycoprotein D, glycoprotein I, or glycoprotein E, including mutants, derivatives, variants, comparable equivalents, or functional analogs, or a combination thereof of a herpes simplex virus 2 (HSV2).
  • the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, glycoprotein 34 (gp34), glycoprotein 68 (gp68), UL128, UL130, UL131A, or UL16, including mutants, derivatives, variants, comparable equivalents, or functional analogs, or a combination thereof of a cytomegalovirus (CMV).
  • CMV cytomegalovirus
  • the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, glycoprotein 350 (gp350), glycoprotein 220 (gp220), or glycoprotein 42 (gp42), including mutants, derivatives, variants, comparable equivalents, or functional analogs, or a combination thereof of a Epstein-Barr virus (EBV).
  • EBV Epstein-Barr virus
  • the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, or glycoprotein N, including mutants, derivatives, variants, comparable equivalents, or functional analogs, or a combination thereof of a varicella-zoster virus (VZV).
  • VZV varicella-zoster virus
  • the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, or glycoprotein N, including mutants, derivatives, variants, comparable equivalents, or functional analogs, or a combination thereof of a human herpesvirus 6 (HHV6).
  • HHV6 human herpesvirus 6
  • the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, or glycoprotein N, including mutants, derivatives, variants, comparable equivalents, or functional analogs, or a combination thereof of a human herpesvirus 7 (HHV7).
  • HHV7 human herpesvirus 7
  • the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, or glycoprotein N, including mutants, derivatives, variants, comparable equivalents, or functional analogs, or a combination thereof of a Kaposi’s sarcoma-associated herpesvirus (KSHV).
  • Glycoprotein B (gB) is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, or glycoprotein N, including mutants, derivatives, variants, comparable equivalents, or functional analogs, or a combination thereof of a Kaposi’s sarcoma-associated herpesvirus (KSHV).
  • the target peptide is obtained or derived from glycoprotein B of a herpesvirus.
  • the glycoprotein B is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • Exemplary glycoprotein B includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 2567-2614, 2615-2623, 2624-2639, 2640-2737, 2738-2746, 2747 , 2748-2783, or 2784-2795 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • HSV1 herpes simplex virus 1
  • HSV2 herpes simplex virus 2
  • VZV varicella-zoster virus
  • CMV cytomegalovirus
  • the glycoprotein B shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the glycoprotein B is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • the target peptide is obtained or derived from glycoprotein H of a herpesvirus.
  • the glycoprotein H is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • Exemplary glycoprotein H includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 2796-2860, 2861-2869, 2870-2885, 2886-2967, 2968-2972, 2973, 2974-2982, or 2983-2997 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • HSV1 herpes simplex virus 1
  • HSV2 herpes simplex virus 2
  • VZV varicella-zoster virus
  • CMV cytomegalovirus
  • the glycoprotein H shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the glycoprotein H is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • the target peptide is obtained or derived from glycoprotein L of a herpesvirus.
  • the glycoprotein L is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • Exemplary glycoprotein L includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 2998-3034, 3035-3037, 3038-3049, 3050-3103, 3104-3108, 3109, 3110-3123, or 3124-3127 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • HSV1 herpes simplex virus 1
  • HSV2 herpes simplex virus 2
  • VZV varicella-zoster virus
  • CMV cytomegalovirus
  • HHV6 human
  • the glycoprotein L shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the glycoprotein L is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • Glycoprotein M (gM)
  • the target peptide is obtained or derived from glycoprotein M of a herpesvirus.
  • the glycoprotein M is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • Exemplary glycoprotein M includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 3128-3170, 3171-3173, 3174-3187, 3188-3231, 3232-3233, 3234, 3235-3262, or 3263-3267 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • HSV1 herpes simplex virus 1
  • HSV2 herpes simplex virus 2
  • VZV varicella-zoster virus
  • CMV cytomegalovirus
  • the glycoprotein M shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the glycoprotein M is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • Glycoprotein N (gN)
  • the target peptide is obtained or derived from glycoprotein N of a herpesvirus.
  • the glycoprotein N is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • Exemplary glycoprotein N includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 3268-3283, 3284-3285, 3286-3292, 3293-3327, 3328-3229, 3330, 3331-3344, or 3345-3349 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • HSV1 her
  • the glycoprotein N shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the glycoprotein N is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • Glycoprotein C (gC)
  • the target peptide is obtained or derived from glycoprotein C of a herpesvirus, for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2).
  • a herpesvirus for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2).
  • the glycoprotein C is a full length protein or a fragment thereof of a herpesvirus, for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • a herpesvirus for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • Exemplary glycoprotein C includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 3350-3413 or 3414-3418 of a herpesvirus, for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • a herpesvirus for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • HSV1 herpes simplex virus 1
  • HSV2 herpes simplex virus 2
  • the glycoprotein C shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof. Given the amino acid sequences of the glycoprotein C, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above glycoprotein C. Such DNA or RNA sequences are deemed to be incorporated in this disclosure.
  • the glycoprotein C is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • Glycoprotein D (gD)
  • the target peptide is obtained or derived from glycoprotein D of a herpesvirus, for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2).
  • a herpesvirus for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2).
  • the glycoprotein D is a full length protein or a fragment thereof of a herpesvirus, for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • a herpesvirus for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • Exemplary glycoprotein D includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 3419-3444 or 3445-3446 of a herpesvirus, for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • a herpesvirus for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • HSV1 herpes simplex virus 1
  • HSV2 herpes simplex virus 2
  • the glycoprotein D shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the glycoprotein D is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • the target peptide is obtained or derived from glycoprotein I of a herpesvirus, for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2).
  • the glycoprotein I is a full length protein or a fragment thereof of a herpesvirus, for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • Exemplary glycoprotein I includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 3447-3521 or 3522-3529 of a herpesvirus, for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • a herpesvirus for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • HSV1 herpes simplex virus 1
  • HSV2 herpes simplex virus 2
  • the glycoprotein I shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the glycoprotein I is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • Glycoprotein E (gE)
  • the target peptide is obtained or derived from glycoprotein E of a herpesvirus, for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2).
  • a herpesvirus for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2).
  • the glycoprotein E is a full length protein or a fragment thereof of a herpesvirus, for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • a herpesvirus for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • Exemplary glycoprotein E includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 15725-16107 or 16108-16386 of a herpesvirus, for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the glycoprotein E shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the glycoprotein E is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • Glycoprotein 350 (gp350)
  • the target peptide is obtained or derived from glycoprotein 350 of a herpesvirus, for example, Epstein-Barr virus (EBV).
  • a herpesvirus for example, Epstein-Barr virus (EBV).
  • the glycoprotein 350 is a full length protein or a fragment thereof of a herpesvirus, for example, Epstein-Barr virus (EBV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • a herpesvirus for example, Epstein-Barr virus (EBV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • EBV Epstein-Barr virus
  • Exemplary glycoprotein 350 includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 3530-3554 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the glycoprotein 350 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the glycoprotein 350 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • Glycoprotein 220 (gp220)
  • the target peptide is obtained or derived from glycoprotein 220 of a herpesvirus, for example, Epstein-Barr virus (EBV).
  • the glycoprotein 220 is a full length protein or a fragment thereof of a herpesvirus, for example, Epstein-Barr virus (EBV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • Exemplary glycoprotein 220 includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 19093-19096 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the glycoprotein 220 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the glycoprotein 220 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • the target peptide is obtained or derived from glycoprotein 42 of a herpesvirus, for example, Epstein-Barr virus (EBV).
  • EBV Epstein-Barr virus
  • the glycoprotein 42 is a full length protein or a fragment thereof of a herpesvirus, for example, Epstein-Barr virus (EBV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • EBV Epstein-Barr virus
  • Exemplary glycoprotein 42 includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 3555-3557 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the glycoprotein 42 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the glycoprotein 42 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • Glycoprotein 34 (gp34)
  • the target peptide is obtained or derived from glycoprotein 34 of a herpesvirus, for example, cytomegalovirus (CMV).
  • a herpesvirus for example, cytomegalovirus (CMV).
  • the glycoprotein 34 is a full length protein or a fragment thereof of a herpesvirus, for example, cytomegalovirus (CMV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • CMV cytomegalovirus
  • Exemplary glycoprotein 34 includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 16387-16680 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the glycoprotein 34 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the glycoprotein 34 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • Glycoprotein 68 (gp68)
  • the target peptide is obtained or derived from glycoprotein 68 of a herpesvirus, for example, cytomegalovirus (CMV).
  • CMV cytomegalovirus
  • the glycoprotein 68 is a full length protein or a fragment thereof of a herpesvirus, for example, cytomegalovirus (CMV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • CMV cytomegalovirus
  • Exemplary glycoprotein 68 includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 16681-17065 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof. In some embodiments, the glycoprotein 68 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the glycoprotein 68 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • the target peptide is obtained or derived from UL128 of a herpesvirus, for example, cytomegalovirus (CMV).
  • a herpesvirus for example, cytomegalovirus (CMV).
  • the UL128 is a full length protein or a fragment thereof of a herpesvirus, for example, cytomegalovirus (CMV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • CMV cytomegalovirus
  • Exemplary UL128 includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 17066-17435 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the UL128 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the UL128 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • the target peptide is obtained or derived from UL130 of a herpesvirus, for example, cytomegalovirus (CMV).
  • CMV cytomegalovirus
  • the UL130 is a full length protein or a fragment thereof of a herpesvirus, for example, cytomegalovirus (CMV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • Exemplary ULI 30 includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 17436-18255 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the UL130 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the UL130 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • the target peptide is obtained or derived from UL131A of a herpesvirus, for example, cytomegalovirus (CMV).
  • a herpesvirus for example, cytomegalovirus (CMV).
  • the UL131A is a full length protein or a fragment thereof of a herpesvirus, for example, cytomegalovirus (CMV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • CMV cytomegalovirus
  • Exemplary UL131A includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 18256-18687 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the UL131A shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the UL131A is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • the target peptide is obtained or derived from ULI 6 of a herpesvirus, for example, cytomegalovirus (CMV).
  • a herpesvirus for example, cytomegalovirus (CMV).
  • the ULI 6 is a full length protein or a fragment thereof of a herpesvirus, for example, cytomegalovirus (CMV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • CMV cytomegalovirus
  • Exemplary UL16 includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 18688-19092 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the UL16 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the UL16 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • the target peptide is obtained or derived from regulatory protein of a herpesvirus.
  • the regulatory protein is obtained or derived from herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicellazoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), Kaposi’s sarcoma-associated herpesvirus (KSHV), or a combination thereof.
  • the regulatory protein is selected from the group comprising multifunctional regulatory of expression, DNA polymerase, DNA polymerase processivity subunit, helicase-primase ATPase subunit, helicase-primase RNA pol subunit B, helicase- primase subunit C, single strand DNA binding protein, alkaline deoxyribonuclease, deoxyuridine triphosphatase, uracil-DNA glycosidase, ribonucleotide reductase large subunit, ribonucleotide reductase subunit 2, EBNA1, EBNA2, EBNA3, LMP1, LMP2, maturational protease, assembly protein, capsid transport nuclear protein, terminase ATPase subunit 1, terminase DNA binding subunit 2, terminase binding protein, nuclear egress membrane protein, nuclear egress lamina protein, including mutants, derivatives, variants, comparable equivalents, functional analogs, or a combination
  • the target peptide is obtained or derived from multifunctional regulator of expression of a herpesvirus, for example, human herpesvirus 6 (HHV6).
  • HHV6 human herpesvirus 6
  • the multifunctional regulator of expression is a full length protein or a fragment thereof of a herpesvirus, for example, human herpesvirus 6 (HHV6) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • HHV6 human herpesvirus 6
  • Exemplary multifunctional regulator of expression includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 3558-3560 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the multifunctional regulator of expression shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the multifunctional regulator of expression is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • the target peptide is obtained or derived from ribonucleotide reductase large subunit of a herpesvirus, for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2).
  • a herpesvirus for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2).
  • the ribonucleotide reductase large subunit is a full length protein or a fragment thereof of a herpesvirus, for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2), or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • a herpesvirus for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2), or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • Exemplary ribonucleotide reductase large subunit includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 3561-3634 or 3635-3645 of herpesvirus, for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • herpes simplex virus 1 HSV1
  • HSV2 herpes simplex virus 2
  • the ribonucleotide reductase large subunit shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the ribonucleotide reductase large subunit is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • the target peptide is obtained or derived from ribonucleotide reductase subunit 2 of a herpesvirus, for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2).
  • a herpesvirus for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2).
  • the ribonucleotide reductase subunit 2 is a full length protein or a fragment thereof of a herpesvirus, for example, herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • a herpesvirus for example, herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • Exemplary ribonucleotide reductase subunit 2 includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 3646-3670 or 3671-3673 of a herpesvirus, for example, herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • HSV1 herpes simplex virus 1
  • HSV2 herpes simplex virus 2
  • the ribonucleotide reductase subunit 2 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the ribonucleotide reductase subunit 2 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • the target peptide is obtained or derived from EBNA1 of herpesvirus, for example, Epstein-Barr virus (EBV).
  • EBV Epstein-Barr virus
  • the EBNA1 is a full length protein or a fragment thereof of a herpesvirus, for example, Epstein-Barr virus (EBV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • a herpesvirus for example, Epstein-Barr virus (EBV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • EBV Epstein-Barr virus
  • Exemplary EBNA1 includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 3674-3684 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the EBNA1 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the EBNA1 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • the target peptide is obtained or derived from EBNA2 of a herpesvirus, for example, Epstein-Barr virus (EBV).
  • EBV Epstein-Barr virus
  • the EBNA2 is a full length protein or a fragment thereof of a herpesvirus, for example, Epstein-Barr virus (EBV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • a herpesvirus for example, Epstein-Barr virus (EBV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • EBV Epstein-Barr virus
  • Exemplary EBNA2 includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 3685-3694 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the EBNA2 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the EBNA2 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • the target peptide is obtained or derived from EBNA3 of a herpesvirus, for example, Epstein-Barr virus (EBV).
  • EBV Epstein-Barr virus
  • the EBNA3 is a full length protein or a fragment thereof of a herpesvirus, for example, Epstein-Barr virus (EBV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • a herpesvirus for example, Epstein-Barr virus (EBV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • EBV Epstein-Barr virus
  • Exemplary EBNA3 includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 3695-4008 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the EBNA3 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the EBNA3 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • the target peptide is obtained or derived from LMP1 of herpesvirus, for example, Epstein-Barr virus (EBV).
  • LMP1 is a full length protein or a fragment thereof of a herpesvirus, for example, Epstein-Barr virus (EBV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • Exemplary LMP1 includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 4009-4017 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the LMP1 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the LMP1 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • the target peptide is obtained or derived from LMP2 of herpesvirus, for example, Epstein-Barr virus (EBV).
  • EBV Epstein-Barr virus
  • the LMP2 is a full length protein or a fragment thereof of a herpesvirus, for example, Epstein-Barr (EBV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • EBV Epstein-Barr
  • Exemplary LMP2 includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 4018-4032 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the LMP2 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the LMP2 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • the target peptide is obtained or derived from maturational protease of a herpesvirus, for example, human herpesvirus 6 (HHV6) or human herpesvirus 7 (HHV7).
  • a herpesvirus for example, human herpesvirus 6 (HHV6) or human herpesvirus 7 (HHV7).
  • Exemplary maturational protease includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 4033-4034 or 4035 of a herpesvirus, for example, human herpesvirus 6 (HHV6) or human herpesvirus 7 (HHV7) respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • HHV6 human herpesvirus 6
  • HHV7 human herpesvirus 7
  • the maturational protease shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the maturational protease is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • the target peptide is obtained or derived from assembly protein of a herpesvirus, for example, human herpesvirus 7 (HHV7).
  • HHV7 human herpesvirus 7
  • Exemplary assembly protein includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NO: 4036 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the assembly protein shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the assembly protein is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • the target peptide is obtained or derived from nuclear egress membrane protein of a herpesvirus, for example, Epstein-Barr virus (EBV).
  • EBV Epstein-Barr virus
  • the nuclear egress membrane protein is a full length protein or a fragment thereof of a herpesvirus, for example, an Epstein-Barr virus (EBV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.
  • EBV Epstein-Barr virus
  • the nuclear egress membrane protein shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.
  • the nuclear egress membrane protein is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • the target peptide is obtained or derived from DNA polymerase of a herpesvirus or comparable equivalents, including the codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the DNA polymerase is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutant, derivatives, variants, or functional analogs thereof.
  • the target peptide is obtained or derived from DNA polymerase processivity subunit of a herpesvirus or comparable equivalents, including the codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the DNA polymerase processivity subunit is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutant, derivatives, variants, or functional analogs thereof.
  • the target peptide is obtained or derived from helicase - primase ATPase subunit of a herpesvirus or comparable equivalents, including the codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the helicase-primase ATPase subunit is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutant, derivatives, variants, or functional analogs thereof.
  • the target peptide is obtained or derived from alkaline deoxyribonuclease of a herpesvirus or comparable equivalents, including the codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the alkaline deoxyribonuclease is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutant, derivatives, variants, or functional analogs thereof.
  • the target peptide is obtained or derived from deoxyuridine triphosphatase of a herpesvirus or comparable equivalents, including the codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the deoxyuridine triphosphatase is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutant, derivatives, variants, or functional analogs thereof.
  • the target peptide is obtained or derived from capsid transport nuclear protein of a herpesvirus or comparable equivalents, including the codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the capsid transport nuclear protein is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutant, derivatives, variants, or functional analogs thereof.
  • the target peptide is obtained or derived from terminase ATPase subunit 1 of a herpesvirus or comparable equivalents, including the codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the terminase ATPase subunit 1 is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutant, derivatives, variants, or functional analogs thereof.
  • the target peptide is obtained or derived from terminase DNA binding subunit 2 of a herpesvirus or comparable equivalents, including the codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the terminase DNA binding subunit 2 is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutant, derivatives, variants, or functional analogs thereof.
  • the target peptide is obtained or derived from terminase binding protein of a herpesvirus or comparable equivalents, including the codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the terminase binding protein is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutant, derivatives, variants, or functional analogs thereof.
  • the target peptide is obtained or derived from nuclear egress lamina protein of a herpesvirus or comparable equivalents, including the codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the nuclear egress lamina protein is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutant, derivatives, variants, or functional analogs thereof.
  • the target peptide is obtained or derived from B cell epitope of a herpesvirus, including a fragment, mutant, derivative or variant thereof.
  • Exemplary B cell epitopes include, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 4042-4261, 4262-4546, 4547-4582, 4583-5034, 5035-5041, 5042-5043, 5044-7725, or 7726-7752 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • HSV1 herpes simplex virus 1
  • HSV2 herpes simplex virus 2
  • VZV varicella-zoster virus
  • CMV cytome
  • the B cell epitopes share at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the B cell epitopes are encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • the target peptide is obtained or derived from T cell epitope of a herpesvirus, including a fragment, mutant, derivative or variant thereof.
  • Exemplary T cell epitopes include, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 7753-8033, 8034-8293, 8294-8742, 8743-10004, 10005-14658, 14659-14660, 14661-15312, or 15313-15724 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the T cell epitopes share at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid
  • the T cell epitopes are encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.
  • the multisubunit nucleic acid sequence and multisubunit peptide includes selfassembling sequence and self-assembling peptide respectively.
  • the self-assembling sequence comprises of a sequence of nucleotides, either deoxyribonucleotides or ribonucleotides, that encodes a self-assembling peptide.
  • the self-assembling sequence includes codon optimized sequences, fragments, mutants, variants, comparable equivalents, functional analogs, or a combination thereof.
  • the selfassembling sequence is a DNA, an RNA, or an mRNA.
  • Any self-assembling peptide that is capable of self-assembling into a polypeptide nanoparticle can be employed in accordance with the present disclosure.
  • self-assembling peptide is a full-length protein or its fragment, mutants, or variant thereof.
  • the self-assembling peptide includes, but not limited to, lumazine synthase, MS2 coat protein, hepatitis B surface antigen (HBsAg) from Hepatitis B Virus, hepatitis B core antigen (HbcAg) from Hepatitis B virus, human papillomavirus LI (HPV LI) protein, matrix protein Ml from influenza A virus, ferritin, riboflavin synthase, a dihydrolipoyl acetyltransferase (E2p), or a combination thereof, including their codon optimized nucleic acid sequences, fragments, mutants, variants, comparable equivalent, or functional analogs thereof.
  • HBsAg hepatitis B surface antigen
  • HbcAg hepatitis B core antigen
  • HPV LI human papillomavirus LI
  • matrix protein Ml from influenza A virus
  • ferritin ferritin
  • riboflavin synthase a di
  • the self-assembling peptide is a ferritin peptide.
  • Ferritin is one of the ubiquitous proteins found in nature. It is produced by all living organisms including archaea, bacteria, algae, higher plants, and animals. Each ferritin protein is generally composed of 12 or 24 subunits or peptides which selfassembles into a ferritin nanoparticle.
  • the multisubunit nucleic acid sequence and multisubunit peptide includes ferritin sequence and ferritin peptide respectively.
  • the ferritin sequence comprises of a sequence of nucleotides, either deoxyribonucleotides or ribonucleotides, that encodes a ferritin peptide.
  • the ferritin sequence is a DNA or an RNA or an mRNA.
  • ferritin peptide that is capable of self-assembling into a nanoparticle can be employed in accordance with the present disclosure.
  • the ferritin peptide is obtained or derived from Helicobacter pylori ferritin, including their codon optimized nucleic acid sequences, fragments, mutants, variants, comparable equivalents, or functional analogs thereof.
  • the ferritin peptide is obtained or derived from Listeria innocua ferritin, including their codon optimized nucleic acid sequences, fragments, mutants, variants, comparable equivalents, or functional analogs thereof.
  • the self-assembling peptide is lumazine synthase.
  • the lumazine synthase is obtained or derived from Aquifex species (for example, Aquifex aeolicus) or Bacillus species (for example, Bacillus subtil is), including their codon optimized nucleic acid sequences, fragments, mutants, variants, comparable equivalents, or functional analogs thereof.
  • the self-assembling peptide is dihydrolipoyl acetyltransferase (E2p).
  • the dihydrolipoyl acetyltransferase (E2p) is obtained or derived from Bacillus stearothermophilus, including their codon optimized nucleic acid sequences, fragments, mutants, variants, comparable equivalents, or functional analogs thereof.
  • the self-assembling peptide is MS2 coat protein. In some embodiments, the self-assembling peptide is MS2 coat protein obtained or derived from Emesvirus zinderi, including their codon optimized nucleic acid sequences, fragments, mutants, variants, comparable equivalents, or functional analogs thereof.
  • Exemplary self-assembling peptides includes, but not limited to, the ones represented by the following amino acid sequences or comparable equivalents, or a combination thereof, including codon optimized sequences, fragments, mutants, variants, or functional analogs thereof: LSKDIIKLLNEQVNKEMNSSNLYMSMSSWCYTHSLDGAGLFLFDHAAEEYEHAK KLIIFLNENNVPVQLTSISAPEHKFEGLTQIFQKAYEHEQHISESINNIVDHAIKSKDH ATFNFLQWYVAEQHEEEVLFKDILDKIELIGNENHGLYLADQYVKGI (SEQ ID NO: 1);
  • AKRKKRKL (SEQ ID NO: 9):
  • GLLKDGNPIPSAIAANSGIY (SEQ ID NO: 19097);
  • GIVTTENIEQAIETAGTKAGNKGVDCAVSAIEMANLQRSFE (SEQ ID NO: 19099):
  • the self-assembling peptide shares at least 50% identity with the sequences described herein above or comparable equivalents, or a combination thereof, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the self-assembling peptide is encoded by the self-assembling sequence which may be either a DNA, an RNA, or an mRNA.
  • the multisubunit nucleic acid sequence and multisubunit peptide includes linker sequence and linker peptide respectively.
  • the linker sequence comprises a sequence of nucleotides, either deoxyribonucleotides or ribonucleotides, that encodes a linker peptide.
  • the linker sequence includes codon optimized sequences, fragments, mutants, variants, comparable equivalents, functional analogs, or a combination thereof.
  • the linker sequence is a DNA, an RNA, or an mRNA.
  • the linker peptide connects the target peptide with the selfassembling peptide in a polypeptide. In some embodiments, the linker peptide connects the signal peptide with a polypeptide. In some other embodiments, the linker peptide connects the signal peptide with the first polypeptide. In some embodiments, one linker peptide connects the cleavage peptide with the target peptide and another linker peptide connects the target peptide with the self-assembling peptide in a polypeptide. In some embodiments, the linker peptide connects two cleavage peptides. Any suitable linker peptides can be employed in accordance with the present disclosure.
  • the linker peptide is an amino acid linker, a zipper motif, a foldon, a scaffold or a combination thereof. In some embodiments, the linker peptide is an amino acid linker. In some embodiments, the linker peptide is a zipper motif. In some embodiments, the linker peptide is a foldon. In some embodiments, the linker peptide is a scaffold. In some embodiments, the linker peptide comprises a combination of an amino acid linker and a zipper motif. In some embodiments, the linker peptide comprises a combination of an amino acid linker and a foldon. In some embodiments, the linker peptide comprises a combination of an amino acid linker and a scaffold.
  • the linker peptide comprises a combination of a zipper motif and a foldon. In some embodiments, the linker peptide comprises a combination of a zipper motif and a scaffold. In some embodiments, the linker peptide comprises a combination of a foldon and a scaffold. In some embodiments, the linker peptide comprises a combination of an amino acid linker, a zipper motif, and a scaffold. In some embodiments, the linker peptide comprises a combination of an amino acid linker, a foldon, and a scaffold. In some embodiments, the linker peptide comprises a combination of a zipper motif, a foldon, and a scaffold.
  • the linker peptide comprises a combination of a zipper motif, a foldon, and a scaffold. In some embodiments, the linker peptide comprises a combination of an amino acid linker, a zipper motif, a foldon, and a scaffold.
  • the amino acid linker comprises of about 2-49 amino acids, 2-40 amino acids, 2-30 amino acids, 2-20 amino acids, 2-15 amino acids, or 2-10 amino acids.
  • the amino acid linker comprises a glycine serine linker, a glycine proline linker, a glycine threonine linker, an alanine serine linker, any combination of two amino acid, or a combination thereof.
  • the glycine proline linker comprises of glycine (G) and proline (P) amino acids consecutively without any preference of order of appearance of either glycine or proline.
  • the glycine proline linker is 2-49 amino acids in length.
  • the glycine threonine linker comprises of glycine (G) and threonine (T) amino acids consecutively without any preference of order of appearance of either glycine or threonine.
  • the glycine threonine linker is 2-49 amino acids in length.
  • the alanine serine linker comprises of alanine (A) and serine (S) amino acids consecutively without any preference of order of appearance of either alanine or serine.
  • the alanine serine linker is 2-49 amino acids in length.
  • the glycine serine linker comprises of glycine (G) and serine (S) amino acids consecutively without any preference of order of appearance of either glycine or serine.
  • the glycine serine linker is 2-49 amino acids in length.
  • amino acid linkers include, but not limited to, the ones represented by the following amino acid sequences or comparable equivalents, or their combinations, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof:
  • GSGG SEQ ID NO: 13
  • GGSGG SEQ ID NO: 14
  • GGSGGGGSGGGGSGG SEQ ID NO: 16
  • the amino acid linkers share at least 50% identity with the sequences described herein above or comparable equivalents, or a combination thereof, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the amino acid linker is encoded by an amino acid linker sequence which may be either a DNA, an RNA, or an mRNA.
  • linker peptide is a zipper motif.
  • a zipper motif comprises of a sequence of amino acids encoded by a zipper sequence.
  • Zipper motifs are generally a class of protein-protein interaction domains that facilitates formation of a complex i.e., enables two, three, four, five, or six homologous or heterologous polypeptides to associate themselves into a polypeptide cluster.
  • the zipper motif is a leucine zipper, an isoleucine zipper, or any synthetic zipper.
  • Exemplary zipper motifs include, but not limited to, the ones represented by the following amino acid sequences or comparable equivalents, or a combination thereof, including codon optimized sequences, fragments, mutants, variants, or functional analogs thereof:
  • RNAYLRKKIARLKKDNLQLERDEQNLEKIIANLRDEIARLENEVA SEQ ID NO: 19104;
  • the zipper motif shares at least 50% identity with the sequences described herein above or comparable equivalents, or a combination thereof, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the zipper motif is encoded by a zipper sequence which may be either a DNA, an RNA or an mRNA.
  • the linker peptide is a foldon.
  • a foldon comprises of a sequence of amino acids encoded by a foldon sequence.
  • the foldon sequence includes codon optimized sequences, fragments, mutants, variants, functional analogs, or a combination thereof.
  • a foldon enables two or more homologous polypeptides to organise to form an oligomeric complex.
  • foldon also helps in orientation of a polypeptide such that the domains or epitopes on the target peptide are exposed or displayed for interaction or communication with cells or biomolecules or immune system.
  • Exemplary foldons includes, but not limited to, the ones represented by the following amino acid sequences or comparable equivalents, or a combination thereof, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof:
  • the foldon shares at least 50% identity with the sequences described herein above or comparable equivalents, or a combination thereof, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the foldon is encoded by a foldon sequence which may be either a DNA, an RNA, or an mRNA.
  • the linker peptide is a scaffold.
  • a scaffold comprises of a sequence of amino acids encoded by a scaffold sequence.
  • the scaffold sequence includes codon optimized sequences, fragments, mutants, variants, or a combination thereof.
  • a scaffold provides structural and/or functional integrity or support to the target peptide and may also help in orientation of target peptide such that the domains or epitopes of the target peptide are exposed or displayed for interaction or communication with cells or biomolecules or immune system.
  • Exemplary scaffolds include, but not limited to, the ones represented by the following amino acid sequences or comparable equivalents, or a combination thereof, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof:
  • VDNKFNKEMRNAYWEIALLPNLNNQQKRAFIRSLYDDPSQSANLLAEAKKLNDA QAPK (SEQ ID NO: 22);
  • ETDICKLPKDEGTCRDFILKWYYDPNTKSCARFWYGGCGGNENKFGSQKECEKV CAPV (SEQ ID NO: 29); MIPGGLSEAKPATPEIQEIVDKVKPQLEEKTNETYGKLEAVQYKTQVVAGTNYYI KVRAGDNKYMHLKVFKSLPGQNEDLVLTGYQVDKNKDDELTGF (SEQ ID NO: 30);
  • GKCPETFDAWYCLNDAHCFAVLINTNGSWHIVYSCECAIGFMGQRCEYKE SEQ ID NO: 43;
  • FAVESIEKLRNRNGSWEILVKWRGWSPKYNTWEPEENIG (SEQ ID NO: 50); MRDFFVITNSLYNFNGSWYIKGAVLHVSPTQKRAFWVIADQENFIKQVNKNIEYV EKQASPAFLQRIVEIYQVKFEGKNVG (SEQ ID NO: 51).
  • the scaffold shares at least 50% identity with the sequences described herein above or comparable equivalents, or a combination thereof, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the scaffold is encoded by the scaffold sequence which may be either a DNA, an RNA, or an mRNA.
  • the linker peptide comprises an amino acid linker and a zipper motif. In some embodiments, the linker peptide comprises an amino acid linker followed by a zipper motif. In some embodiments, the linker peptide comprises a zipper motif followed by an amino acid linker. In some embodiments, the linker peptide comprises an amino acid linker followed by a zipper motif and another an amino acid linker. In some embodiments, the linker peptide comprises a zipper motif followed by an amino acid linker, and another zipper motif.
  • the linker peptide comprises an amino acid linker and a foldon. In some embodiments, the linker peptide comprises an amino acid linker followed by a foldon. In another embodiment, the linker peptide comprises a foldon followed by an amino acid linker. In some embodiments, the linker peptide comprises an amino acid followed by a foldon and another amino acid linker. In some embodiments, the linker peptide comprises a foldon followed by an amino acid linker and another foldon. In some embodiments, the linker peptide comprises an amino acid linker and a scaffold. In some embodiments, the linker peptide comprises an amino acid linker followed by a scaffold.
  • the linker peptide comprises a scaffold followed by an amino acid linker. In some embodiments, the linker peptide comprises an amino acid linker followed by a scaffold and another amino acid linker. In some embodiments, the linker peptide comprises a scaffold followed by an amino acid linker and another scaffold.
  • the linker peptide comprises a zipper motif and a scaffold. In some embodiments, the linker peptide comprises a zipper motif followed by a scaffold. In some embodiments, the linker peptide comprises a scaffold followed by a zipper motif. In some embodiments, the linker peptide comprises a scaffold followed by a zipper motif and another scaffold. In some embodiments, the linker peptide comprises a zipper motif followed by a scaffold and another zipper motif.
  • the linker peptide comprises a foldon and a scaffold. In some embodiments, the linker peptide comprises a foldon followed by a scaffold. In some embodiments, the linker peptide comprises a scaffold followed by a foldon. In some embodiments, the linker peptide comprises a foldon followed by a scaffold and another foldon. In some embodiments, linker peptide comprises a scaffold followed by a foldon and another scaffold.
  • the linker peptide comprises an amino acid linker, a zipper motif, and a scaffold. In some embodiments, the linker peptide comprises an amino acid linker followed by a zipper motif, and a scaffold. In some embodiments, the linker peptide comprises a zipper motif followed by an amino acid linker, and a scaffold. In some embodiments, the linker peptide comprises a scaffold followed by an amino acid linker, and a zipper motif. In some embodiments, the linker peptide comprises a first amino acid linker followed by a zipper motif, a second amino acid linker followed by a scaffold, and a third amino acid linker.
  • the linker peptide comprises a first amino acid linker followed by a scaffold, a second amino acid linker followed by a zipper motif, and a third amino acid linker. In some embodiments, the linker peptide comprises a scaffold followed by a first amino acid linker, and a zipper motif followed by a second amino acid linker. In some embodiments, the linker peptide comprises a first amino acid linker followed by a scaffold, and a second amino acid linker followed by a zipper motif. In some embodiments, the linker peptide comprises an amino acid linker, a foldon and a scaffold. In some embodiments, the linker peptide comprises an amino acid linker followed by a foldon and a scaffold.
  • the linker peptide comprises a foldon followed by an amino acid linker, and a scaffold. In some embodiments, the linker peptide comprises a scaffold followed by an amino acid linker, and a foldon. In some embodiments, the linker peptide comprises a first amino acid linker followed by a foldon, a second amino acid linker followed by scaffold, and a third amino acid linker. In some embodiments, the linker peptide comprises a first amino acid linker followed by a scaffold, a second amino acid linker followed by a foldon, and a third amino acid linker. In some embodiments, the linker peptide comprises a scaffold followed by a first amino acid linker, and a foldon followed by a second amino acid linker. In some embodiments, the linker peptide comprises a first amino acid linker followed by a scaffold, and a second amino acid linker followed by a foldon.
  • the multisubunit nucleic acid sequence and multisubunit peptide includes cleavage sequence and cleavage peptide respectively.
  • the cleavage sequence comprises of a sequence of nucleotides, either deoxyribonucleotides or ribonucleotides, that encodes a cleavage peptide.
  • the cleavage sequence includes codon optimized sequences, fragments, mutants, variants, comparable equivalents, functional analogs, or a combination thereof.
  • the cleavage sequence is a DNA, an RNA, or an mRNA.
  • the cleavage peptide connects one polypeptide with another polypeptide, for example, the adjacent polypeptide.
  • the cleavage peptide carries one or more cleavage sites.
  • the cleavage peptide comprises one or more cleavage peptides, for example cleavage peptide- 1, cleavage peptide-2 and so on.
  • the cleavage peptide optionally comprises a linker peptide between two cleavage peptides.
  • the cleavage peptide facilitates the action of cellular proteases to cleave the multisubunit polypeptide into individual polypeptides or self cleaves into individual polypeptides.
  • the resulting polypeptides comprises either a target peptide, a linker peptide and a self-assembling peptide or a linker peptide, target peptide, linker peptide and a self-assembling peptide or a combination thereof.
  • the polypeptide in addition to these peptides, may also have some residues (amino acids) of cleavage peptide. Any cleavage peptide that is susceptible to the action of cellular proteases or a cleavage peptide that has the ability to undergo self cleavage can be employed in accordance with the present disclosure.
  • the cleavage peptide is a substrate for cellular proteases. In some embodiments, the cleavage peptide is a substrate for golgi specific proteases. In some embodiments, the cleavage peptide is a self cleaving peptide. In some embodiments, the cleavage peptide comprises two or more cleavage peptides (for example, cleavage peptide- 1, cleavage peptide-2 and so on), optionally linked by a linker peptide, wherein one cleavage peptide is a substrate for cellular proteases and the other cleavage peptide is a self cleaving peptide. In some embodiments, the cleavage peptide is a golgi specific cleavage peptide i.e., susceptible to action of golgi specific proteases.
  • Exemplary cleavage peptide includes, but not limited to, the one represented by the following amino acid sequence or comparable equivalents, or a combination thereof, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof:
  • GIRRKRSVSH (SEQ ID NO: 53);
  • VQREKRAVGI (SEQ ID NO: 54);
  • SIRHKREPSV SEQ ID NO: 55
  • HNRTKRSTDG (SEQ ID NO: 58);
  • RKRRKRELET (SEQ ID NO: 59);
  • NLRRRRDLVD (SEQ ID NO: 62);
  • ATNFSLLKQAGDVEENPGP (SEQ ID NO: 64);
  • the cleavage peptide shares at least 50% identity with the sequence described herein above or comparable equivalents, or a combination thereof, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the cleavage peptide is encoded by a cleavage sequence which may be either a DNA, an RNA, or an mRNA.
  • the multisubunit nucleic acid sequence and multisubunit peptide includes a signal sequence and a signal peptide respectively.
  • the signal sequence comprises of a sequence of nucleotides, either deoxyribonucleotides or ribonucleotides, that encodes a signal peptide.
  • the signal sequence includes codon optimized sequences, fragments, mutants, variants, comparable equivalents, functional analogs, or a combination thereof.
  • the signal sequence is a DNA, an RNA, or an mRNA.
  • the signal peptide is present upstream (N-terminus or amino-terminus) of one or more polypeptides. In some embodiments, the signal peptide is present on the N-terminus of all or some polypeptides. In some embodiments, the signal peptide is present on the N- terminus of the first polypeptide. In some embodiments, the signal peptide is present upstream (N-terminus) of some polypeptides. In some embodiments, the signal peptide is present upstream (N-terminus) of each of the polypeptides.
  • the signal peptide transports the multisubunit peptide to cell organelles. In some embodiments, the signal peptide transports the multisubunit peptide to golgi body or golgi apparatus/complex. Any signal peptide that transports the multisubunit peptide to golgi bodies can be employed in accordance with the present disclosure. In some embodiments, the signal peptide is a golgi targeting signal peptide i.e., directs the multisubunit peptide to golgi complex.
  • Exemplary signal peptide includes, but not limited to, the one represented by the following amino acid sequence or comparable equivalents, or a combination thereof, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof:
  • MPSSVSWGILLLAGLCCLVPVSLAEDPQGDAA (SEQ ID NO: 67); MGSSVSWGILLLAGLCCLVPVSLAEDPQGDAA (SEQ ID NO: 68); MASSVSWGILLLAGLCCLVPVSLAEDPQGDAA (SEQ ID NO: 69);
  • MDWTWRVFCLLAVTPGAHP (SEQ ID NO: 72);
  • MAWSPLFLTLITHCAGSWA (SEQ ID NO: 73);
  • MSRLFVFILIALFLSAIIDVMS (SEQ ID NO: 77);
  • MGMRMMFIMFMLVVLATTVVS (SEQ ID NO: 78);
  • MASSLYSFLLALSIVYIFVAPTHS (SEQ ID NO: 81);
  • MKAAQILTASIVSLLPIYTSA (SEQ ID NO: 84);
  • MIKLKFGVFFTVLLSSAYA SEQ ID NO: 85
  • MGVKVLFALICIAVAEA (SEQ ID NO: 86).
  • the signal peptide shares at least 50% identity with the sequence described herein above or comparable equivalents, or a combination thereof, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.
  • the signal peptide is encoded by a signal sequence which may be either a DNA, an RNA, or an mRNA.
  • Multisubunit nucleic acid sequence according to the present disclosure can be either a DNA or an RNA or an mRNA.
  • the multisubunit nucleic acid sequence as described herein can be synthesized by molecular biology or genetic engineering techniques well known in the art, for example, using recombinant expression system, chemical synthesis, or in vitro transcription (IVT).
  • the multisubunit nucleic acid sequence is obtained through a single IVT process or step. In some embodiments, the multisubunit nucleic acid sequence obtained through single IVT process or step is an mRNA. In some embodiments, the multisubunit nucleic acid sequence is obtained or synthesized through a single in vitro transcription (IVT) process or step.
  • IVTT in vitro transcription
  • the multisubunit nucleic acid sequence is a messenger RNA (mRNA).
  • mRNA messenger RNA
  • the mRNA encodes a multisubunit peptide as described herein.
  • an mRNA typically includes at least a coding region (which encodes the multisubunit peptide), a 5’ UTR, a 3’ UTR, a 5’ cap and a 3’ poly(A) tail.
  • UTR untranslated regions
  • the 5’ UTR and the 3’ UTR are sections of the mRNA before the start codon and after the stop codon respectively.
  • the 5’ UTR has a cap (5’ cap) consisting of altered nucleotides.
  • mRNA also contains a poly adenylated region at its 3’ end having adenine nucleotides called poly(A) tail.
  • the mRNA is unmodified or modified or a combination of both.
  • the modification may be in the nucleobase of the nucleotide, or sugar moiety of the nucleotide, or the phosphate of the nucleotide.
  • unmodified mRNA comprises naturally occurring nucleosides, for example, adenosine, guanosine, cytidine, and uridine.
  • mRNA comprises one or more modified nucleosides, for example, adenosine analog, guanosine analog, cytidine analog, or uridine analog.
  • the one or more modified nucleosides is a nucleoside analog selected from 2-aminoadenosine, 3-methyl adenosine, 7-deazaadenosine, 7- deazaguanosine, 8-oxoadenosine, or 8-oxoguanosine or a combination thereof.
  • the one or more modified nucleosides is a uridine analog selected from propynyl-uridine, pseudouridine, C5 -bromouridine, C5-fluorouridine, C5- iodouridine, C5-propynyl-uridine, 5-aza-uridine, 2-thio-5-aza-uridine, 2-thio-uridine, 4- thio-pseudouridine, 2-thio-pseudouridine, 5-hydroxy-uridine, 3-methyl-uridine, 5- carboxymethyl-uridine, 1 -carboxymethyl-pseudouridine, l-methyl-3-(3-amino-3- carboxypropyl)pseudouridine, 2-thio-2 ’ -O-methyl-uridine, 5 -methoxycarbonylmethyl-2 ’ - O-methyl-uridine, 5-carboxymethylaminomethyl-2 ’ -O-methyl-uridine, 3 ,2 ’ -O
  • the one or more modified nucleosides is a cytidine analog selected from 5-methylcytidine, C5-propynyl-cytidine, C5-methylcytidine, pseudoisocytidine, 1-methyl-pseudoisocytidine, pyrrolo-pseudoisocytidine, 4-thio- pseudoisocytidine, 4-thio- 1 -methyl-pseudoisocytidine, 4-thio- 1 -methyl- 1 -deaza- pseudoisocytidine, 1 -methyl- 1-1 deaza-pseudoisocytidine, 4-methoxy- 1 -methyl- pseudoisocytidine, or a combination thereof.
  • the modified nucleoside is pseudouridine, for example, 1- methyl-pseudouridine, 1-propynyl-pseudouridine, 1-carboxymethyl-pseudouridine, 1- methyl-3-(3-amino-3-carboxypropyl)pseudouridine, 4-methoxy-pseudouridine, or 4- methoxy-2-thio-pseudouridine 4-thio-pseudouridine, 2-thio-pseudouridine, 4-thio-l- methyl-pseudouridine, 2-thio- 1-methyl-pseudouridine, dihydro-pseudouridine, or a combination thereof.
  • pseudouridine for example, 1- methyl-pseudouridine, 1-propynyl-pseudouridine, 1-carboxymethyl-pseudouridine, 1- methyl-3-(3-amino-3-carboxypropy
  • mRNA is produced using recombinant expression system, chemically synthesized, or obtained through in vitro transcription.
  • the multisubunit nucleic acid sequence is obtained or synthesized through a single IVT process or step.
  • mRNAs according to the present disclosure may be synthesized via in vitro transcription (IVT). Briefly, IVT is typically performed with a DNA template containing a promoter, a pool of ribonucleotide triphosphates, a buffer system that may include DTT and magnesium ions, and an appropriate RNA polymerase (e.g., T3, T7, or SP6 RNA polymerase), DNase I, pyrophosphatase, and/or RNase inhibitor. The exact conditions may vary according to the specific application.
  • RNA polymerase e.g., T3, T7, or SP6 RNA polymerase
  • the in vitro transcription occurs in a single batch.
  • IVT reaction includes capping and tailing reactions either co- transcriptionally or separately.
  • a cap analog is added to the in vitro transcription reaction and will be incorporated at the 5’ end of the mRNA during the reaction.
  • Alternative method of capping involves adding the cap post-transcriptionally through an enzymatic reaction.
  • the poly (A) tail can be incorporated into the DNA template sequence, and thus the poly (A) tail will be incorporated into the mRNA by T7 RNA polymerase during the in vitro transcription.
  • Alternative method of tailing involves adding the poly (A) tail post- transcriptionally through an enzymatic reaction.
  • capping and tailing reactions are performed co-transcriptionally i.e., during the IVT reaction. In some embodiments, capping and tailing reactions are performed separately from IVT reaction i.e., post transcriptionally.
  • mRNA produced as a result of IVT reaction may be purified using techniques well known in the art, such as, centrifugation, filtration and/or chromatographic techniques. The purification of mRNA may be accomplished before capping and tailing steps are performed or after capping and tailing.
  • the synthesized mRNA may be purified by ethanol precipitation or filtration or chromatography methods. In some embodiments, tangential flow filtration is used to purify mRNA.
  • mRNA is purified by chromatographic step. In other embodiments, mRNA is purified by a combination of filtration and chromatography steps.
  • a suitable mRNA sequence is an mRNA sequence encoding a protein, peptide, polypeptide.
  • a suitable mRNA sequence is codon optimized for efficient expression in a host cell or organism. Codon optimization typically includes modifying a naturally-occurring or wild-type nucleic acid sequence encoding a peptide, polypeptide, or protein to achieve the highest possible expression of peptide, polypeptide, protein, or an antibody without altering the amino acid sequence.
  • the mRNA is circular. In other embodiments, the mRNA is linear.
  • the mRNA is self-amplifying or self-replicating.
  • mRNA is few hundred nucleotides long to several thousand nucleotides long. In some embodiments, mRNA is about 0.5 kb, 1 kb, 1.5 kb, 2 kb, 2.5 kb, 3 kb, 3.5 kb, 4 kb, 4.5 kb, 5 kb, 5.5 kb, 6 kb, 6.5 kb, 7.0 kb, 7.5 kb, 8 kb, 8.5 kb, 9 kb, 9.5 kb, 10 kb, 10.5 kb, 11 kb, 11.5 kb, 12 kb, 12.5 kb, 13 kb, 13.5 kb, 14 kb, 14.5 kb, 15 kb, 16 kb, 17 kb, 18 kb, 19 kb, 20 kb, 21 kb, 22 kb, 23 kb, 24 kb, 25 kb, 26 kb
  • mRNA is about 0.5 to 30 kb, 0.5 to 25 kb, 0.5 to 20 kb in length, or any range therein. In some embodiments, mRNA is about 1 to 20 kb, 1 to 18 kb, 1 to 16 kb, 1 to 14 kb, 1 to 12 kb, 1 to 10 kb, 1 to 9 kb, 1 to 8 kb, 1 to 7 kb, 1 to 6 kb, 1 to 5 kb in length, or any range therein.
  • mRNA is about 0.5 kb to about 1 kb, about 1 kb to about 2 kb, about 2 kb to about 3 kb, about 3 kb to about 4 kb, about 4 kb to about 5 kb, about 5 kb to about 6 kb, about 6 kb to about 7 kb, about 7 kb to about 8 kb, about 8 kb to about 9 kb, about 9 kb to about 10 kb, about 10 kb to about 11 kb, about 11 kb to about 12 kb, about 12 kb to about 13 kb, about 13 kb to about 14 kb, about 14 kb to about 15 kb, about 15 kb to about 16 kb, about 16 kb to about 17 kb, about 17 kb to about 18 kb, about 18 kb to about 19 kb, about 19 kb to about 20 kb, about 20 kb
  • the multisubunit nucleic acid sequence as described herein, express multisubunit peptide.
  • the multisubunit peptide, encoded by the multisubunit nucleic acid comprises multiple repeats of polypeptide comprising either a target peptide, a linker peptide, and a self-assembling peptide or a linker peptide, target peptide, a linker peptide, and a selfassembling peptide, or a combination thereof, interspersed with cleavage peptide (see illustration in figures), wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • the total number of polypeptides present in a multisubunit peptide are up to 100 polypeptides.
  • one or more polypeptides in the multisubunit peptide has identical target peptides (homologous polypeptides).
  • one or more polypeptides in the multisubunit peptide has different target peptides (heterologous polypeptides).
  • a multisubunit peptide as described herein is encoded by the multisubunit nucleic acid sequence as described herein.
  • Each multisubunit peptide comprises two or more polypeptides, wherein some or all polypeptides comprises either a target peptide, a linker peptide, and a self-assembling peptide or a linker peptide, a target peptide, a linker peptide, and a self-assembling peptide or a combination thereof, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • the polypeptides are connected with each other through a cleavage peptide.
  • the multisubunit peptide includes a signal peptide upstream (N-terminus) of one or more polypeptides. In some embodiments, the multisubunit peptide includes a signal peptide upstream (N- terminus) of each of all or some polypeptides. In some embodiments, the multisubunit peptide optionally includes a signal peptide upstream (N-terminus) of each polypeptide. In some embodiments, the multisubunit peptide includes a signal peptide upstream (N- terminus) of some polypeptides. In some embodiments, the multisubunit peptide includes a signal peptide upstream (N-terminus) of all polypeptides.
  • the signal peptide transports the multisubunit peptide to golgi body or golgi apparatus.
  • the cellular proteases act on the cleavage sites present in the cleavage peptides or the cleavage peptide undergoes self cleavage and cleaves the multisubunit peptide into individual polypeptides comprising either a target peptide, a linker peptide, and a selfassembling peptide, or a linker peptide, a target peptide, a linker peptide, and a selfassembling peptide, or a signal peptide, a target peptide, a linker peptide, and a selfassembling peptide, or a signal peptide, a linker peptide, a target peptide, a linker peptide, and a selfassembling peptide, or a signal peptide, a linker peptide, a target peptide, a linker peptide, and a
  • the linker peptide is an amino acid linker, a zipper motif, a foldon, a scaffold, or a combination thereof.
  • polypeptides are homologous polypeptides.
  • two or more homologous polypeptides organise to form an oligomeric complex.
  • the oligomeric complex comprises at least two homologous polypeptides, at least three homologous polypeptides, at least four homologous polypeptides, at least five homologous polypeptides, or at least six homologous polypeptides and so on.
  • polypeptides are heterologous polypeptides.
  • the homologous polypeptides or the heterologous polypeptides organise to form a polypeptide cluster.
  • a polypeptide nanoparticle is formed by self-assembly of two or more homologous polypeptides, two or more heterologous polypeptides, one or more oligomeric complexes, one or more polypeptide clusters, or their combination.
  • a polypeptide nanoparticle comprises homologous polypeptides, heterologous polypeptides, oligomeric complexes, polypeptide clusters, or a combination thereof.
  • the polypeptide nanoparticles are symmetrical, non- symmetrical, asymmetrical, or a combination thereof.
  • the polypeptide nanoparticles are icosahedral, helical, spherical, rod-like, or a combination thereof.
  • the polypeptide nanoparticles are enveloped or nonenveloped or a combination thereof.
  • the polypeptide nanoparticles are single layered or multilayered or a combination thereof.
  • the polypeptide nanoparticle comprises at least 2 or up to 500 polypeptides.
  • the polypeptide nanoparticle comprises polypeptides between 2-5, 2-10, 2-20, 20-40, 40-60, 60-80, 80-100, 100-120, 120-140, 140-160, 160- 180, 180-200, 200-220, 220-240, 240-260, 260-280, 280-300, 300-320, 320-340, 340-360, 360-380, 380-400, 400-420, 420-440, 440-460, 460-480, or 480-500.
  • the polypeptide nanoparticle comprises polypeptides between 2-5, 2-10, 10-20, 20-30, 30-40, 40-50, 50-60, 60-70, 70-80, 80-90, or 90-99.
  • the polypeptide nanoparticle comprises at least 2 or up to 500 homologous polypeptides.
  • the polypeptide nanoparticle comprises at least 2 or up to 500 heterologous polypeptides.
  • the polypeptide nanoparticle comprises two or more oligomeric complexes such that the total number of polypeptides in the polypeptide nanoparticle are not more than 500.
  • the polypeptide nanoparticle comprises two or more polypeptide clusters such that the total number of polypeptides in the polypeptide nanoparticle are not more than 500.
  • the polypeptide nanoparticle comprises some homologous polypeptides and some heterologous polypeptides such that the total number of polypeptides in the polypeptide nanoparticle are not more than 500.
  • the polypeptide nanoparticle comprises some homologous polypeptides and some oligomeric complexes such that the total number of polypeptides in the polypeptide nanoparticle are not more than 500.
  • the polypeptide nanoparticle comprises some heterologous polypeptides and some oligomeric complexes such that the total number of polypeptides in the polypeptide nanoparticle are not more than 500.
  • the polypeptide nanoparticle comprises some homologous polypeptides and some polypeptide clusters such that the total number of polypeptides in the polypeptide nanoparticle are not more than 500.
  • the polypeptide nanoparticle comprises some heterologous polypeptides and some polypeptide clusters such that the total number of polypeptides in the polypeptide nanoparticle are not more than 500.
  • the polypeptide nanoparticle comprises some polypeptide clusters and some oligomeric complexes such that the total number of polypeptides in the polypeptide nanoparticle are not more than 500.
  • the polypeptide nanoparticle comprises some homologous polypeptides, some heterologous polypeptides, some oligomeric complexes, or their combination such that the total number of polypeptides in the polypeptide nanoparticle are not more than 500.
  • the polypeptide nanoparticle comprises some homologous polypeptides, some heterologous polypeptides, some polypeptide clusters, or their combination such that the total number of polypeptides in the polypeptide nanoparticle are not more than 500. In some embodiments, the polypeptide nanoparticle comprises some homologous polypeptides, some polypeptide clusters, some oligomeric complexes, or their combination such that the total number of polypeptides in the polypeptide nanoparticle are not more than 500.
  • the polypeptide nanoparticle comprises some heterologous polypeptides, some polypeptide clusters, some oligomeric complexes, or their combination such that the total number of polypeptides in the polypeptide nanoparticle are not more than 500.
  • the polypeptide nanoparticle comprises some heterologous polypeptides, some homologous polypeptides, some polypeptide clusters, some oligomeric complexes, or their combination such that the total number of polypeptides in the polypeptide nanoparticle are not more than 500.
  • Lipid nanoparticles (LNP) composition Lipid nanoparticles (LNP) composition
  • the multisubunit nucleic acid sequences as described herein may be encapsulated or formulated in a lipid nanoparticle composition.
  • the lipid nanoparticle composition comprises lipid components, ionizable polymer, or a combination thereof and a multisubunit nucleic acid sequence as described herein.
  • the lipid nanoparticle composition comprises lipid components such as a cationic lipid, a phospholipid, a sterol, a PEG-lipid and a multisubunit nucleic acid sequence as described herein.
  • the lipid nanoparticle composition comprises an ionizable polymer, a cationic lipid, a phospholipid, a sterol, a PEG-lipid and a multisubunit nucleic acid sequence as described herein.
  • a vaccine comprising the lipid nanoparticle composition is provided herein.
  • Lipid components of the lipid nanoparticle compositions may include one or more lipids, such as a cationic lipid, a phospholipid, a sterol, and a PEG-lipid.
  • lipids such as a cationic lipid, a phospholipid, a sterol, and a PEG-lipid.
  • Cationic lipid refers to a lipid that has a net positive charge at a selected pH.
  • Cationic lipids generally comprise a hydrophilic head group that carries the charge and a hydrophobic tail.
  • the cationic lipid is a cationic lipid with an amine head group.
  • the amine head group can be primary, secondary, tertiary or quaternary.
  • the cationic lipid may comprise one (monoamine) or more (polyamine) such amine groups.
  • the cationic lipids are positively charged at pH below the pKa of the cationic lipid. In certain embodiments, the cationic lipids are neutral i.e., when pH is same or above the pKa of the cationic lipid. In some embodiments, the cationic lipids are positively charged at acidic pH i.e., pH 1.0 to pH 6.9. In certain embodiments, the cationic lipids are neutral at certain pH i.e., around physiological pH (pH 7.0 to pH 7.5). A cationic lipid that can exist in a positively charged or neutral form depending on the pH is commonly referred to as ionizable lipid. In some embodiments, the cationic lipids are ionizable such that they can exist in a positively charged or neutral form depending on the pH. In some embodiments, the cationic lipids are positively charged irrespective of the pH.
  • the cationic lipid present in the lipid nanoparticle composition comprises a cationic lipid disclosed in US provisional applications viz., 63/575930; 63/575934; 63/575938; 63/575939; and 63/575942.
  • the cationic lipid present in the lipid nanoparticle composition comprises a cationic lipid represented by formula (I) formula (I) or isomer, or salt thereof, wherein:
  • Ri and R2 are independently chosen from H, -OH, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, C5-10 heteroaryl containing 1-4 heteroatoms, -O-L7-R5, and -NReR?, or Ri and R2 may combine together to form a saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, or C5-10 heteroaryl containing 1-4 heteroatoms;
  • R3 and R4 are independently chosen from branched or unbranched C1-26 alkyl, C2-26 alkenyl, C2-26 alkynyl, -(CH 2 ) m -A-(CH 2 )n-(CH3) y , and -CH((CH 2 )m-A-(CH 2 )n-(CH3) y )2, wherein each of m, n, and y is independently an integer ranging from 0 to 26;
  • Rs, Re, and R7 are independently chosen from H, -OH, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, and C5-10 heteroaryl containing 1-4 heteroatoms; each of Li, L2, L3, L4, L5, Le, and L7 is either absent or independently chosen from C1-10 alkylene, C2-10 alkenylene, and C2-10 alkynylene;
  • Xi and X2 are independently chosen from -C(O)O-, -OC(O)-, -C(O)NH-, -NHC(O)-, - C(S)NH-, -NHC(S)-, -C(S)O-, -OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, and - OP(O)(O-)O-;
  • A is H, a bond, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, or C5-10 heteroaryl containing 1-4 heteroatoms; C(S)O-, -OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, S, or N provided that when Ai is -CH 2 -, -C(O)O-, -OC(O)-, -C(O)NH-, -NHC(O)-, -C(S)NH-, -NHC(S)-, -C(S)O-, - OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, or S, one of Ri or R 2 is absent; and wherein each alkyl, al
  • the cationic lipid present in the lipid nanoparticle composition comprises a cationic lipid represented by formula (II) formula (II) or isomer, or salt thereof, wherein:
  • Ri and R2 are independently chosen from H, -OH, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, C5-10 heteroaryl containing 1-4 heteroatoms, -O-L7-R5, and -NReR?, or
  • Ri and R2 may combine together to form a saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, or C5-10 heteroaryl containing 1-4 heteroatoms;
  • R3 and R4 are independently chosen from, branched or unbranched, C1-26 alkyl, C2-26 alkenyl, C2-26 alkynyl, -(CH2)m-A-(CH2)n-(CH 3 ) y , and -CH((CH2)m-A-(CH2)n-(CH 3 ) y )2, wherein each of m, n, and y is independently an integer ranging from 0 to 26;
  • Rs, Re, and R7 are independently chosen from H, -OH, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, and C5-10 heteroaryl containing 1-4 heteroatoms; each of Li, L2, L3, L4, Ls, Le, and L7 is either absent or independently chosen from C1-10 alkylene, C2-10 alkenylene, and C2-10 alkynylene;
  • Xi and X2 are independently chosen from -C(O)O-, -OC(O)-, -C(O)NH-, -NHC(O)-, - C(S)NH-, -NHC(S)-, -C(S)O-, -OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, and - OP(O)(O-)O-;
  • A is H, a bond, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, or C5-10 heteroaryl containing 1-4 heteroatoms; C(S)O-, -OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, S, or N provided that when Ai is -CH 2 -, -C(O)O-, -OC(O)-, -C(O)NH-, -NHC(O)-, -C(S)NH-, -NHC(S)-, -C(S)O-, - OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, or S, one of Ri or R 2 is absent; and wherein each alkyl, al
  • Ri and R2 are independently chosen from H, -OH, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, C5-10 heteroaryl containing 1-4 heteroatoms, -O-L7-R5, and -NReR?, or
  • Ri and R2 may combine together to form a saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, or C5-10 heteroaryl containing 1-4 heteroatoms;
  • R3 and R4 are independently chosen from branched or unbranched C1-26 alkyl, C2-26 alkenyl, C2-26 alkynyl, -(CH 2 ) m -A-(CH 2 )n-(CH3) y , and -CH((CH 2 )m-A-(CH 2 )n-(CH3) y )2, wherein each of m, n, and y is independently an integer ranging from 0 to 26;
  • Rs, Re, and R7 are independently chosen from H, -OH, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, and C5-10 heteroaryl containing 1-4 heteroatoms; each of Li, L2, L3, L4, L5 Le, and L7 is either absent or independently chosen from C1-10 alkylene, C2-10 alkenylene, and C2-10 alkynylene;
  • Xi and X2 are independently chosen from -C(O)O-, -OC(O)-, -C(O)NH-, -NHC(O)-, - C(S)NH-, -NHC(S)-, -C(S)O-, -OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, and - OP(O)(O-)O-;
  • A is H, a bond, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatom, or C5-10 heteroaryl containing 1-4 heteroatom; C(S)O-, -OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, S, or N provided that when Ai is -CH
  • the cationic lipid present in the lipid nanoparticle composition comprises a cationic lipid represented by formula (IV) formula (IV) or isomer, or salt thereof, wherein:
  • Ri and R 2 are independently chosen from H, -OH, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, C5-10 heteroaryl containing 1-4 heteroatoms, -O-L7-R5, and -NReR?, or
  • Ri and R 2 may combine together to form a saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, or C5-10 heteroaryl containing 1-4 heteroatoms;
  • R3 and R4 are independently chosen from branched or unbranched C1-26 alkyl, C 2.2 6 alkenyl, C 2.26 alkynyl, -(CH 2 ) m -A-(CH 2 )n-(CH 3 ) y , and -CH((CH 2 ) m -A-(CH 2 )n-(CH 3 ) y ) 2 , wherein each of m, n, and y is independently an integer ranging from 0 to 26;
  • Rs, Re, and R7 are independently chosen from H, -OH, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, and C5-10 heteroaryl containing 1-4 heteroatoms; each of Li, L2, L3, L4, Ls, Le, and L7 is either absent
  • Xi and X2 are independently chosen from -C(O)O-, -OC(O)-, -C(O)NH-, -NHC(O)-, - C(S)NH-, -NHC(S)-, -C(S)O-, -OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, and - OP(O)(O-)O-;
  • A is H, a bond, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatom, or C5-10 heteroaryl containing 1-4 heteroatom; C(S)O-, -OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, S, or N provided that when Ai is -CH 2 -, -C(O)O-, -OC(O)-, -C(O)NH-, -NHC(O)-, -C(S)NH-, -NHC(S)-, -C(S)O-, - OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, or S, one of Ri or R 2 is absent; and wherein each alkyl, alkeny
  • the cationic lipid present in the lipid nanoparticle composition comprises a cationic lipid represented by formula (V) formula (V) or isomer, or salt thereof, wherein:
  • R3 and R4 are independently chosen from branched or unbranched C1-26 alkyl, C2-26 alkenyl, C2-26 alkynyl, -(CH 2 ) m -A-(CH 2 )n-(CH3) y , and -CH((CH 2 )m-A-(CH 2 )n-(CH3) y )2, wherein each of m, n, and y is independently an integer ranging from 0 to 26; (Rio)qis chosen from H, -OH, optionally substituted Ci-io alkyl, C2-10 alkenyl, C2-10 alkynyl, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, C5-10 heteroaryl containing 1-4 heteroatoms, -O-L7-R5, and -NReR?, wherein q is an integer ranging from 0 to
  • Rs, Re, and R7 are independently chosen from H, -OH, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, and C5-10 heteroaryl containing 1-4 heteroatoms; each of Li, L2, L3, L4, and L7 is either absent or independently chosen from C1-10 alkylene, C2-10 alkenylene, and C2-10 alkynylene;
  • Xi and X2 are independently chosen from -C(O)O-, -OC(O)-, -C(O)NH-, -NHC(O)-, - C(S)NH-, -NHC(S)-, -C(S)O-, -OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, and - OP(O)(O-)O-;
  • A is H, a bond, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, or C5-10 heteroaryl containing 1-4 heteroatoms; and wherein each alkyl, alkenyl, alkynyl, alkylene, alkenylene, alkynylene, cycloalkyl, aryl, heterocycloalkyl, heteroaryl is independently optionally substituted with one or more substituent.
  • the cationic lipid present in the lipid nanoparticle composition comprises a cationic lipid represented by formula (VI) formula (VI) or isomer, or salt thereof, wherein:
  • R3 and R4 are independently chosen from branched or unbranched C1-26 alkyl, C2-26 alkenyl, C2-26 alkynyl, -(CH 2 )m-A-(CH2)n-(CH 3 ) y , and -CH((CH 2 )m-A-(CH2)n-(CH 3 ) y )2, wherein each of m, n, and y is independently an integer ranging from 0 to 26; each of Li, L2, L3, and L4 is either absent or independently chosen from C1-10 alkylene, C2- 10 alkenylene, and C2-10 alkynylene; Xi and X2 are independently chosen from -C(O)O-, -OC(O)-, -C(O)NH-, -NHC(O)-, - C(S)NH-, -NHC(S)-, -C(S)O-, -OC(S)-, -OC(O)NH-, -
  • A is H, a bond, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, or C5-10 heteroaryl containing 1-4 heteroatoms; and wherein each alkyl, alkenyl, alkynyl, alkylene, alkenylene, alkynylene, cycloalkyl, aryl, heterocycloalkyl, heteroaryl is independently optionally substituted with one or more substituent.
  • the cationic lipid present in the lipid nanoparticle composition comprises a cationic lipid represented by formula (VII) formula (VII) or isomer, or salt thereof, wherein:
  • R3 and R4 are independently chosen from, branched or unbranched, C1-26 alkyl, C2-26 alkenyl, C2-26 alkynyl, -(CH2)m-A-(CH2)n-(CH 3 ) y , and -CH((CH2)m-A-(CH2)n-(CH 3 ) y )2, wherein each of m, n, and y is independently an integer ranging from 0 to 26;
  • (Rio)q is chosen from H, -OH, -CH2OH, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, C5-10 heteroaryl containing 1-4 heteroatoms, -O-Ls-Rs, and - NReR?, wherein q is an integer ranging from 0 to 5;
  • R7 are independently chosen from H, -OH, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, and C5-10 heteroaryl containing 1-4 heteroatoms; each of Li, L2, L3, L4, L5, L7, and Ls is either absent or independently chosen from C1-10 alkylene, C2-10 alkenylene, and C2-10 alkynylene; Xi and X2 are independently chosen from -C(O)O-, -OC(O)-, -C(O)NH-, -NHC(O)-, - C(S)NH-, -NHC(S)-, -C(S)O-, -OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(
  • A is H, a bond, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, or C5-10 heteroaryl containing 1-4 heteroatoms;
  • Z is -CH 2 -, O, N, or S;
  • Ai is -CH2-, -C(O)O-, -OC(O)-, -C(O)NH-, -NHC(O)-, -C(S)NH-, -NHC(S)-, -C(S)O-, - OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, S, or N; and wherein each alkyl, alkenyl, alkynyl, alkylene, alkenylene, alkynylene, cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is independently optionally substituted with one or more substituent.
  • the cationic lipid present in the lipid nanoparticle composition comprises a cationic lipid represented by formula (VIII) formula (VIII) or isomer, or salt thereof, wherein:
  • R3 and R4 are independently chosen from branched or unbranched C1-26 alkyl, C2-26 alkenyl, C2-26 alkynyl, -(CH 2 ) m -A-(CH 2 )n-(CH3) y , and -CH((CH 2 )m-A-(CH 2 )n-(CH3) y )2, wherein each of m, n, and y is independently an integer ranging from 0 to 26;
  • (Rio)q is chosen from H, -OH, -CH2OH, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, C5-10 heteroaryl containing 1-4 heteroatoms, -O-Ls-Rs, and - NReR?, wherein q is an integer ranging from 0 to 4;
  • Rs, Re, and R7 are independently chosen from H, -OH, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, and C5-10 heteroaryl containing 1-4 heteroatoms; each of Li, L2, L3, L4, L5, L7, and Ls is either absent or independently chosen from C1-10 alkylene, C2-10 alkenylene, or C2-10 alkynylene;
  • Xi and X2 are independently chosen from -C(O)O-, -OC(O)-, -C(O)NH-, -NHC(O)-, - C(S)NH-, -NHC(S)-, -C(S)O-, -OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, and - OP(O)(O-)O-;
  • A is H, a bond, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, or C5-10 heteroaryl containing 1-4 heteroatoms;
  • Z is -CH2-, O, N, or S
  • Ai is -CH 2 -, -C(O)O-, -OC(O)-, -C(O)NH-, -NHC(O)-, -C(S)NH-, -NHC(S)-, -C(S)O-, - OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, S, or N; and wherein each alkyl, alkenyl, alkynyl, alkylene, alkenylene, alkynylene, cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is independently optionally substituted with one or more substituent.
  • the cationic lipid represented by formula (I), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), or formula (VIII) are substituted with substituents independently chosen from H, OH, Cl, Br, I, O, S, N, P, optionally substituted C1-6 alkoxy, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted saturated or unsaturated C3-10 cycloalkyl, optionally substituted Ce-io aryl, optionally substituted saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, optionally substituted C5-10 heteroaryl containing 1-4 heteroatoms or combination thereof.
  • substituent may further be substituted with H, -OH, Cl, Br, I, or Ci- 6 hydroxyalkyl.
  • N:P ratio or cationic lipid to nucleic acid ratio in LNP formulation is between 1 to 18, between 1 to 17, between 1 to 16, between 1 to 15, between 1 to 14, between 1 to 13, between 1 to 12, between 1 to 11, between 1 to 10, between 1 to 9, between 1 to 8, between 1 to 7, between 1 to 6, between 1 to 5, between 1 to 4, between 1 to 3, between 1 to 2, or any range therein.
  • N:P ratio or cationic lipid to nucleic acid ratio in LNP formulation is about 18, about 17, about 16, about 15, about 14, about 13, about 12, about 11, about 10, about 9, about 8, about 7, about 6, about 5, about 4, about 3, about 2, about 1, or any portion or fraction thereof.
  • other exemplary cationic lipid for use in the lipid nanoparticle compositions include, but are not limited to, N,N-dioleyl-N,N- dimethylammonium chloride (DODAC); N-(2,3-dioleyloxy)propyl)-N,N,N- trimethylammonium chloride (DOTMA); N,N-distearyl-N,N-dimethylammonium bromide(DDAB); N-(2,3dioleoyloxy)propyl)-N,N,N-trimethylammonium chloride (DOTAP); 3-(N — (N’,N’-dimethylaminoethane)-carbamoyl)cholesterol (DC-Chol), N-(l- (2,3-dioleoyloxy)propyl)N-2-(sperminecarboxamido)ethyl)-N,N- dimethylammoniumtrifluoracetate (DOSPA), dioc
  • DODAC
  • Methods of making cationic lipid and/or ionizable lipid or imparting the cationic lipid the ability to behave as an ionizable lipid are well known in the art (WO2005121348; W02009127060; W02009086558; W02010042877; W02010144740; WO2011075656; WO2017049245; WO2017075531; WO2018118102; WO2015199952; ReynierP. et al. Journal of Drug Targeting (2004) 12: 25-38; Sabnis, Staci et al. Molecular Therapy (2016) 26: 1509-1519).
  • the cationic lipid present in the lipid nanoparticle composition comprises a cationic lipid disclosed in published patent application viz., WO2019/152557; WO2019/232095; WO2021/077067; WO2019/089828; US2019/0240354; US2010/0130588 ; US2021/0087135; US2021/0128488 ; US2020/0121809; US2013/0108685; US2013/0195920; US2015/0005363; US2014/0308304; US 2017/0210697; and US2013/0053572.
  • the proportion of cationic lipid present in the lipid nanoparticle compositions is from about 10 mol % to about 70 mol % or any range therein.
  • the proportion of cationic lipid present in the lipid nanoparticle compositions is from about 10 mol % to about 70 mol %, from about 10 mol % to about 65 mol %, from about 10 mol % to about 60 mol %, from about 10 mol % to about 55 mol %, from about 10 mol % to about 50 mol %, or any range therein.
  • the proportion of cationic lipid present in the lipid nanoparticle compositions is about 10 mol %, about 11 mol %, about 12 mol %, about 13 mol %, about 14 mol %, about 15 mol %, about 16 mol %, about 17 mol %, about 18 mol %, about 19 mol %, about 20 mol %, about 21 mol %, about 22 mol %, about 23 mol %, about 24 mol %, about 25 mol %, about 26 mol %, about 27 mol %, about 28 mol %, about 29 mol %, about 30 mol %, about 31 mol %, about 32 mol %, about 33 mol %, about 34 mol %, about 35 mol %, about 36 mol %, about 37 mol %, about 38 mol %, about 39 mol %, about 40 mol %, about 41 mol %, about 42 mol %, about 40 mol
  • the proportion of cationic lipid present in the lipid nanoparticle compositions is about 10 mol% to about 20 mol%, about 20 mol% to about 30 mol%, about 30 mol% to about 40 mol%, about 40 mol% to about 50 mol%, about 50 mol% to about 60 mol%, about 60 mol% to about 70 mol%, or any range therein.
  • Phospholipid includes a lipid containing a hydrophilic head with a phosphate group and a hydrophobic tail composed of fatty acid chains attached to a glycerol or sphingosine backbone.
  • Exemplary phospholipids for use in the lipid nanoparticle compositions include, but are not limited to, l,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC), 1,2- dimyristoyl-sn-glycero-phosphocholine (DMPC), 1 ,2-dioleoyl-sn-glycero-3- phosphocholine (DOPC), l,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2- distearoyl-sn-glycero-3-phosphocholine (DSPC), 1 ,2-diundecanoyl-sn-glycero- phosphocholine (DUPC), l-palmitoyl-2-
  • the proportion of phospholipid present in the lipid nanoparticle compositions is from about 2 mol % to about 65 mol %, from about 5 mol % to about 65 mol %, from about 10 mol % to about 65 mol %, from about 10 mol % to about 55 mol %, from about 10 mol % to about 50 mol %, or any range therein.
  • the proportion of phospholipid present in the lipid nanoparticle compositions is about 65 mol %, about 60 mol %, about 55 mol %, about 50 mol %, about 45 mol %, about 44 mol %, about 43 mol %, about 42 mol %, about 41 mol %, about 40 mol %, about 39 mol %, about 38 mol %, about 37 mol %, about 36 mol %, about 35 mol %, about 34 mol %, about 33 mol %, about 32 mol %, about 31 mol %, about 30 mol %, about 29 mol %, about 28 mol %, about 27 mol %, about 26 mol %, about 25 mol %, about 24 mol %, about 23 mol %, about 22 mol %, about 21 mol %, about 20 mol %, about 19 mol %, about 18 mol %, about 17 mol %, about 16
  • Lipid nanoparticle composition disclosed herein may include sterol and/or sterol derivatives.
  • sterol as used herein include, but not limited to, cholesterol, sitosterol, fecosterol, ergosterol, campesterol, stigmasterol or their derivatives.
  • lipid nanoparticle composition comprises cholesterol and/or cholesterol derivatives.
  • Non- limiting examples of cholesterol and cholesterol derivatives include 5 a- cholestanol, 5P-coprostanol, cholesteryl-(2’-hydroxy)-ethyl ether, cholesteryl- (4’- hydroxy)-butyl ether, 6-ketocholestanol, 5a-cholestane, cholestenone, 5a-cholestanone, 5P-cholestanone, cholesteryl decanoate, or mixtures thereof.
  • Methods of making cholesterol and cholesterol derivatives are well known in the art.
  • the proportion of sterol present in the lipid nanoparticle compositions may be from about 20 mol % to about 65 mol % or any range therein.
  • the proportion of sterol present in the lipid nanoparticle compositions is from about 20 mol % to about 65 mol %, from about 25 mol % to about 65 mol %, from about 30 mol % to about 65 mol %, from about 31 mol % to about 60 mol %, from about 32 mol % to about 60 mol %, from about 33 mol % to about 60 mol %, from about 34 mol % to about 60 mol %, from about 35 mol % to about 60 mol %, or any range therein.
  • the proportion of sterol present in the lipid nanoparticle compositions is about 65 mol %, about 60 mol %, about 55 mol %, about 50 mol %, about 45 mol %, about 44 mol %, about 43 mol %, about 42 mol %, about 41 mol %, about 40 mol %, about 39 mol %, about 38 mol %, about 37 mol %, about 36 mol %, about 35 mol %, about 34 mol %, about 33 mol %, about 32 mol %, about 31 mol %, about 30 mol %, about 29 mol %, about 28 mol %, about 27 mol %, about 26 mol %, about 25 mol %, about 24 mol %, about 23 mol %, about 22 mol %, about 21 mol %, about 20 mol %, or any portion or fraction thereof.
  • PEG-lipid, pegylated lipid, PEG linked lipid, PEG conjugated lipid, PEG- lipid conjugate, PEG modified lipid have been used interchangeably to mean polyethylene glycol linked to a lipid moiety.
  • the lipid moiety may be linked directly to the PEG molecule or through a linker.
  • a PEG-lipid comprises a PEG- modified phosphatidylethanolamines, PEG-modified phosphatidic acids, PEG-modified ceramides, PEG-modified dialkylamines, PEG-modified diacylglycerols, PEG-modified dialkylglycerols, and/or PEG-modified cholesterol, and/or mixtures thereof.
  • the methods of making PEG-lipid are well known to persons skilled in the art.
  • PEG-lipid is selected from mPEG-Dimyristoyl glycerol (mPEG-DMG), mPEG-N,N-Ditetradecylacetamide (mPEG-DTA or ALC0159), mPEG- Cholesterol (mPEG-CLS), mPEG-DSPE, mPEG-DMPE, mPEG-DPPE, mPEG-DLPE, mPEG-DOPE, mPEG-DPPC, mPEG-DSPC, l,2-Distearoyl-sn-Glycero-3- Phosphoethanolamine with conjugated methoxyl poly(ethylene glycol) (mPEG-DSPE), l,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000 (mPEG2000-DMG), a- (3 ’ - ⁇ [ 1 ,2-di(myristyloxy)propanoxy]carbony
  • the PEG moiety of the PEG-lipid may comprise an average molecular weight ranging from 0.5 kDa to 10 kDa.
  • the PEG-lipid has an average molecular weight of about 0.5 kDa to 5 kDa, about 0.5 kDa to 4 kDa, 0.5 kDa to 3 kDa, 0.5 kDa to 2 kDa.
  • the PEG-lipid has an average molecular weight of about 0.5 kDa to about 2 kDa.
  • the proportion of PEG-lipid present in the lipid nanoparticle compositions may be from about 0.2 mol % to about 2.0 mol % or any range therein.
  • the proportion of PEG-lipid present in the lipid nanoparticle compositions is from about 0.2 mol % to about 2.0 mol %, from about 0.2 mol % to about 1.9 mol %, from about 0.2 mol % to about 1.8 mol %, from about 0.2 mol % to about 1.7 mol %, from about 0.2 mol % to about 1.6 mol %, from about 0.2 mol % to about 1.5 mol %, or any range therein.
  • the proportion of PEG-lipid present in the lipid nanoparticle compositions is about 0.2 mol %, about 0.3 mol %, about 0. 4 mol %, about 0.5 mol %, about 0.6 mol %, about 0.7 mol %, about 0.8 mol %, about 0.9 mol %, about 1.0 mol %, about 1.1 mol %, about 1.2 mol %, about 1.3 mol %, about 1.4 mol %, about 1.5 mol %, about 1.6 mol %, about 1.7 mol %, about 1.8 mol %, about 1.9 mol %, about 2.0 mol %, or any portion or fraction thereof.
  • the lipid nanoparticle composition additionally contains an ionizable polymer.
  • polymer means a compound formed from a plurality of repeating units called monomers. Polymers are produced through a process called polymerization wherein two or more monomers are linked through chemical bonds to form the polymer. In some embodiments, the polymer is branched or unbranched. In some embodiments, the polymer is homopolymer, i.e., comprising same type of repeat units or monomers, or heteropolymer, i.e., comprising more than one type of repeat units or monomers. The terms heteropolymer and copolymer have been used interchangeably herein.
  • Ionizable polymer as used herein means, a polymer that can exist in a positively charged or neutral form depending on the pH of the solution or environment, for example, ionizable polymer will be cationic (positively charged) when pH of the solution is below the pKa of the ionizable polymer and neutral (no charge) when pH of the solution is same or above the pKa of the ionizable polymer.
  • ionizable polymer is positively charge in acidic pH i.e., pH 1.0 to pH 6.9.
  • ionizable polymer is neutral (no charge) around physiological pH (pH 7.0 to pH 7.5).
  • the lipid nanoparticle compositions comprise an ionizable polymer.
  • the ionizable polymer may be selected from a chitosan, chitosan derivatives, cellulose derivatives, a poly-L-lysine (PLL), a protamine, a polyethyleneimine, their derivatives, or a combination thereof.
  • the ionizable polymer is positively charged at acidic pH i.e., pH 1.0 to 6.9 and is neutral around physiological pH (pH 7.0 to 7.5).
  • the proportion of ionizable polymer present in the lipid nanoparticle compositions may be from about 1 mol % to about 25 mol %.
  • the proportion of ionizable polymer present in the lipid nanoparticle compositions is from about 1 mol % to about 25 mol %, from about 1 mol % to about 24 mol %, from about 1 mol % to about 23 mol %, from about 1 mol % to about 22 mol %, from about 1 mol % to about 21 mol %, from about 1 mol % to about 20 mol %, from about 1 mol % to about 19 mol %, from about 1 mol % to about 18 mol %, from about 1 mol % to about 17 mol %, from about 1 mol % to about 16 mol %, from about 1 mol % to about 15 mol %, or any range therein.
  • the proportion of ionizable polymer present in the lipid nanoparticle compositions is about 1 mol %, about 2 mol %, about 3 mol %, about 4 mol %, about 5 mol %, about 6 mol %, about 7 mol %, about 8 mol %, about 9 mol %, about 10 mol %, about 11 mol %, about 12 mol %, about 13 mol %, about 14 mol %, about 15 mol %, about 16 mol %, about 17 mol %, about 18 mol %, about 19 mol %, about 20 mol %, about 21 mol %, about 22 mol %, about 23 mol %, about 24 mol %, about 25 mol %, or any portion or fraction thereof.
  • the preferred ionizable polymer comprises a chitosan, chitosan derivatives, cellulose derivatives, a poly-L-lysine (PLL), a protamine, polyethyleneimine, and/or their derivatives, or a combination thereof.
  • provided herein is a method of beating or preventing a disease, comprising administering to a subject in need thereof the multisubunit nucleic acid sequence as described herein.
  • lipid nanoparticle composition comprising a cationic lipid, a phospholipid, a sterol, a PEG-lipid and the multisubunit nucleic acid sequence as described herein.
  • a method of heating or preventing a disease comprising administering to a subject in need thereof the lipid nanoparticle composition comprising a cationic lipid, a phospholipid, a sterol, a PEG-lipid and the multisubunit nucleic acid sequence as described herein, wherein the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), or a combination thereof.
  • lipid nanoparticle composition comprising an ionizable polymer, a cationic lipid, a phospholipid, a sterol, a PEG-lipid and the multisubunit nucleic acid sequence as described herein.
  • lipid nanoparticle composition comprising an ionizable polymer, a cationic lipid, a phospholipid, a sterol, a PEG-lipid and the multisubunit nucleic acid sequence as described herein, wherein the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), or a combination thereof.
  • provided herein is a method of treating or preventing a disease, comprising administering to a subject in need thereof a vaccine comprising the multisubunit nucleic acid as described herein.
  • lipid nanoparticle composition comprises a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and the multisubunit nucleic acid as described herein.
  • lipid nanoparticle composition comprises an ionizable polymer, a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and the multisubunit nucleic acid described herein.
  • a method of treating or preventing a disease comprising administering to a subject in need thereof a vaccine comprising the lipid nanoparticle composition, wherein the lipid nanoparticle composition comprises a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and the multisubunit nucleic acid as described herein, wherein the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), or a combination thereof.
  • a method of treating or preventing a disease comprising administering to a subject in need thereof a vaccine comprising the lipid nanoparticle composition, wherein the lipid nanoparticle composition comprises an ionizable polymer, a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and the multisubunit nucleic acid described herein, wherein the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), or a combination thereof.
  • the disclosure relates to use of the multisubunit nucleic acid as described herein, in the manufacture of a medicament for the treatment or prevention of a disease in a subject.
  • the disclosure relates to use of a lipid nanoparticle composition comprising a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and the multisubunit nucleic acid sequence as described herein, in the manufacture of a medicament for the treatment or prevention of a disease in a subject.
  • the disclosure relates to use of a lipid nanoparticle composition comprising a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and the multisubunit nucleic acid sequence as described herein, in the manufacture of a medicament for the treatment or prevention of a disease in a subject, wherein the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), or a combination thereof.
  • the disclosure relates to use of a lipid nanoparticle composition comprising an ionizable polymer, a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and the multisubunit nucleic acid sequence as described herein, in the manufacture of a medicament for the treatment or prevention of a disease in a subject.
  • the disclosure relates to use of a lipid nanoparticle composition comprising an ionizable polymer, a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and the multisubunit nucleic acid sequence as described herein, in the manufacture of a medicament for the treatment or prevention of a disease in a subject, wherein the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), or a combination thereof.
  • the disclosure relates to use of a vaccine comprising multisubunit nucleic acid as described herein, in the manufacture of a medicament for the treatment or prevention of a disease in a subject.
  • the disclosure relates to use of a vaccine comprising a lipid nanoparticle composition, wherein the lipid nanoparticle composition comprises a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and the multisubunit nucleic acid described herein, in the manufacture of a medicament for the treatment or prevention of a disease in a subject.
  • the disclosure relates to use of a vaccine comprising a lipid nanoparticle composition, wherein the lipid nanoparticle composition comprises a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and the multisubunit nucleic acid described herein, in the manufacture of a medicament for the treatment or prevention of a disease in a subject, wherein the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), or a combination thereof.
  • the disclosure relates to use of a vaccine comprising a lipid nanoparticle composition, wherein the lipid nanoparticle composition comprises an ionizable polymer, a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and the multisubunit nucleic acid described herein, in the manufacture of a medicament for the treatment or prevention of a disease in a subject.
  • the lipid nanoparticle composition comprises an ionizable polymer, a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and the multisubunit nucleic acid described herein
  • the disclosure relates to use of a vaccine comprising a lipid nanoparticle composition, wherein the lipid nanoparticle composition comprises an ionizable polymer, a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and the multisubunit nucleic acid described herein, in the manufacture of a medicament for the treatment or prevention of a disease in a subject, wherein the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), or a combination thereof.
  • the disease is gingivostomatitits, genital herpes, herpetic keratitis, herpetic whitlows, neonatal herpes simplex virus infection, herpes simplex encephalitis, varicella or chickenpox, herpes zoster or shingles, congenital cytomegalic inclusion disease, cytomegalovirus mononucleosis, Epstein-Barr virus mononucleosis, exanthem subitem or roseola, or Kaposi sarcoma caused by herpesviruses.
  • the multisubunit nucleic acid sequence is present in biologically effective amount or therapeutically effective amount.
  • the biologically effective amount of the multisubunit nucleic acid sequence is between 0.1 pg to 2000 pg, 0.1 pg to 1800 pg, 0.1 pg to 1600 pg, 0.1 pg to 1400 pg, 0.1 pg to 1200 pg, 0.1 pg to 1000 pg, 0.1 pg to 950 pg, 0.1 pg to 900 pg, 0.1 pg to 850 pg, 0.1 pg to 800 pg, 0.1 pg to 750 pg, 0.1 pg to 700 pg, 0.1 pg to 650 pg, 0.1 pg to 600 pg, 0.1 pg to 550 pg, 0.1 pg to 500 pg, 0.1 pg to 450 pg, 0.1 pg to 400 pg
  • the biologically effective amount of the multisubunit nucleic acid sequence is from about 0.1 pg to 1000 pg, 0.1 pg to 950 pg, 0.1 pg to 900 pg, 0.1 pg to 850 pg, 0.1 pg to 800 pg, 0.1 pg to 750 pg, 0.1 pg to 700 pg, 0.1 pg to 650 pg, 0.1 pg to 600 pg, 0.1 pg to 550 pg, 0.1 pg to 500 pg, or any range therein.
  • the biologically effective amount of the multisubunit nucleic acid sequence is 0.1 pg, 0.2 pg, 0.3 pg, 0.4 pg, 0.5 pg, 0.6 pg, 0.7 pg, 0.8 pg, 0.9 pg, 1 pg, 2 pg, 3 pg, 4 pg, 5 pg, 6 pg, 7 pg, 8 pg, 9 pg, 10 pg, 15 pg, 20 pg, 25 pg, 30 pg, 35 pg, 40 pg, 45 pg, 50 pg, 55 pg, 60 pg, 65 pg, 70 pg, 75 pg, 80 pg, 85 pg, 90 pg, 95 pg, 100 pg, 110 pg, 120 pg, 130 pg, 140 pg, 150 pg, 160 pg, 170 pg, 180 pg
  • a nucleic acid comprising a plurality of polynucleotide sequences, wherein some or all polynucleotide sequences of the plurality comprises either a target sequence, a linker sequence, and a self- assembling sequence or a linker sequence, a target sequence, a linker sequence and a self-assembling sequence or a combination thereof, wherein each polynucleotide sequence of the plurality is connected to an adjacent polynucleotide sequence of the plurality by a cleavage sequence, and wherein the multisubunit nucleic acid further comprises a signal sequence upstream of one or more of the polynucleotide sequences of the plurality, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • a multisubunit nucleic acid comprising a plurality of polynucleotide sequences, wherein each polynucleotide sequence of the plurality comprises a target sequence, a linker sequence, and a self- assembling sequence or a second linker sequence, a second target sequence, a third linker sequence, and a second self-assembling sequence, wherein each polynucleotide sequence of the plurality is connected to an adjacent polynucleotide sequence of the plurality by a cleavage sequence, and wherein the multisubunit nucleic acid further comprises a signal sequence upstream of one or more of the polynucleotide sequences of the plurality, wherein the target sequence or the second target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • a multisubunit nucleic acid comprising a plurality of polynucleotide sequences, wherein each polynucleotide sequence of the plurality comprises a target sequence, a linker sequence, and a self-assembling sequence, wherein each polynucleotide sequence of the plurality is connected to an adjacent polynucleotide sequence of the plurality by a cleavage sequence, and wherein the multisubunit nucleic acid further comprises a signal sequence upstream of one or more of the polynucleotide sequences of the plurality, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • a multisubunit nucleic acid comprising a plurality of polynucleotide sequences, wherein each polynucleotide sequence of the plurality comprises a linker sequence, a target sequence, a linker sequence, and a self-assembling sequence, wherein each polynucleotide sequence of the plurality is connected to an adjacent polynucleotide sequence of the plurality by a cleavage sequence, and wherein the multisubunit nucleic acid further comprises a signal sequence upstream of one or more of the polynucleotide sequences of the plurality, wherein the target sequence is obtained or derived capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • a multisubunit nucleic acid comprising a first plurality of polynucleotide sequences and a second plurality of polynucleotide sequences, each polynucleotide sequence of the first plurality comprises a first target sequence, a first linker sequence, and a first selfassembling sequence, wherein each polynucleotide sequence of the second plurality comprises a second linker sequence, a second target sequence, a third linker sequence, and a second self-assembling sequence, wherein each polynucleotide sequence of the first plurality and each polynucleotide sequence of the second plurality is connected to an adjacent polynucleotide sequence of the first plurality or an adjacent polynucleotide sequence of the second plurality by a cleavage sequence, and wherein the first polynucleotide sequence in the multisubunit nucleic acid is a polynucleotide sequence of the first plurality or a polynucleotide
  • a multisubunit nucleic acid encoding a plurality of polypeptides, wherein some or all polypeptides of the plurality comprises either a target peptide, a linker peptide, and a self-assembling peptide or a linker peptide, a target peptide, a linker peptide and a self-assembling peptide or a combination thereof, wherein each polypeptide of the plurality is connected to an adjacent polypeptide of the plurality by a cleavage peptide, and wherein the multisubunit nucleic acid further encodes a signal peptide on the amino-terminus of one or more of the polypeptides of the plurality, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • a multisubunit nucleic acid encoding a plurality of polypeptides, wherein some or all polypeptides of the plurality comprises either a target peptide, a linker peptide, and a self-assembling peptide or a second linker peptide, a second target peptide, a third linker peptide and a second selfassembling peptide or combination thereof, wherein each polypeptide of the plurality is connected to an adjacent polypeptide of the plurality by a cleavage peptide, and wherein the multisubunit nucleic acid further encodes a signal peptide on the amino-terminus of the first polypeptide of the plurality or the second polypeptide of the plurality or a combination thereof, wherein the target peptide and the second target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus
  • a multisubunit nucleic acid encoding a plurality of polypeptides, wherein each polypeptide of the plurality comprises a target peptide, a linker peptide, and a self-assembling peptide, wherein each polypeptide of the plurality is connected to an adjacent polypeptide of the plurality by a cleavage peptide, and wherein the multisubunit nucleic acid further encodes a signal peptide on the amino-terminus of one or more of the polypeptides of the plurality, wherein the target peptide is obtained or derived capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • a multisubunit nucleic acid encoding a plurality of polypeptides, wherein each polypeptide of the plurality comprises a linker peptide, a target peptide, a linker peptide, and a selfassembling peptide, wherein each polypeptide of the plurality is connected to an adjacent polypeptide of the plurality by a cleavage peptide, and wherein the multisubunit nucleic acid further encodes a signal peptide on the amino-terminus of one or more of the polypeptides of the plurality, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • multisubunit nucleic acid encoding a first plurality of polypeptides and a second plurality of polypeptides, wherein each polypeptide of the first plurality comprises a target peptide, a linker peptide, and a self-assembling peptide, wherein each polypeptide of the second plurality comprises a second linker peptide, a second target peptide, a third linker peptide, and a second self- assembling peptide, wherein each polypeptide of the first plurality and each polypeptide of the second plurality is connected to an adjacent polypeptide of the first plurality or an adjacent polypeptide of the second plurality by a cleavage peptide, and wherein the first polypeptide encoded by the multisubunit nucleic acid is a polypeptide of the first plurality or a polypeptide of the second plurality, and wherein the multisubunit nucleic acid further encodes a signal peptide on the amino-terminus of the first
  • a multisubunit nucleic acid comprising a plurality of polynucleotide sequences, wherein some or all polynucleotide sequences of the plurality comprises either a target sequence, a linker sequence, and a self-assembling sequence or a linker sequence, a target sequence, a linker sequence and a self-assembling sequence or a combination thereof, wherein each polynucleotide sequence of the plurality is connected to an adjacent polynucleotide sequence of the plurality by a cleavage sequence, and wherein the multisubunit nucleic acid further comprises a signal sequence upstream of one or more of the polynucleotide sequences of the plurality, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • a multisubunit nucleic acid comprising a plurality of polynucleotide sequences, wherein each polynucleotide sequence of the plurality comprises a target sequence, a linker sequence, and a self-assembling sequence, wherein each polynucleotide sequence of the plurality is connected to an adjacent polynucleotide sequence of the plurality by a cleavage sequence, and wherein the multisubunit nucleic acid further comprises a signal sequence upstream of one or more of the polynucleotide sequences of the plurality, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • a multisubunit nucleic acid comprising a plurality of polynucleotide sequences, wherein each polynucleotide sequence of the plurality comprises a linker sequence, a target sequence, a linker sequence, and a self-assembling sequence, wherein each polynucleotide sequence of the plurality is connected to an adjacent polynucleotide sequence of the plurality by a cleavage sequence, and wherein the multisubunit nucleic acid further comprises a signal sequence upstream of one or more of the polynucleotide sequences of the plurality, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • a multisubunit nucleic acid encoding a plurality of polypeptides, wherein some or all polypeptides of the plurality comprises either a target peptide, a linker peptide, and a self-assembling peptide or a linker peptide, a target peptide, a linker peptide and a self-assembling peptide or a combination thereof, wherein each polypeptide of the plurality is connected to an adjacent polypeptide of the plurality by a cleavage peptide, and wherein the multisubunit nucleic acid further encodes a signal peptide on the amino-terminus of one or more of the polypeptides of the plurality, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • a multisubunit nucleic acid encoding a plurality of polypeptides, wherein each polypeptide of the plurality comprises a target peptide, a linker peptide, and a selfassembling peptide, wherein each polypeptide of the plurality is connected to an adjacent polypeptide of the plurality by a cleavage peptide, and wherein the multisubunit nucleic acid further encodes a signal peptide on the amino-terminus of one or more of the polypeptides of the plurality, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • a multisubunit nucleic acid encoding a plurality of polypeptides, wherein each polypeptide of the plurality comprises a linker peptide, a target peptide, a linker peptide, and a self-assembling peptide, wherein each polypeptide of the plurality is connected to an adjacent polypeptide of the plurality by a cleavage peptide, and wherein the multisubunit nucleic acid further encodes a signal peptide on the aminoterminus of one or more of the polypeptides of the plurality, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • the multisubunit nucleic acid according to any one of the paragraphs 5-7, wherein the target peptide, the linker peptide, and the self-assembling peptide or the linker peptide, the target peptide, the linker peptide, and the self-assembling peptide are in N-terminus to C-terminus order.
  • the multisubunit nucleic acid according to any one of the preceding paragraphs wherein the herpesvirus is selected from the group comprising herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), Kaposi’s sarcoma-associated herpesvirus (KSHV), or a combination thereof.
  • HSV1 herpes simplex virus 1
  • HSV2 herpes simplex virus 2
  • VZV varicella-zoster virus
  • CMV cytomegalovirus
  • HHV6 human herpesvirus 6
  • HHV7 human herpesvirus 7
  • Epstein-Barr virus EBV
  • Kaposi’s sarcoma-associated herpesvirus KSHV
  • the multisubunit nucleic acid according to paragraph 10 wherein total number of the polynucleotide sequences or the polypeptides are between 2-5, 2-10, 10-20, 20- 30, 30-40, 40-50, 50-60, 60-70, 70-80, 80-90, or 90-99.
  • the multisubunit nucleic acid according to any one of the preceding paragraphs wherein the multisubunit nucleic acid is a DNA or an RNA.
  • the multisubunit nucleic acid according to paragraph 18, wherein the amino acid linker comprises 2 to 49 amino acids.
  • the multisubunit nucleic acid according to paragraph 17, wherein the linker peptide is the foldon.
  • the self-assembling peptide is a lumazine synthase, an MS2 coat protein, a hepatitis B surface antigen (HBsAg) from Hepatitis B Virus, a hepatitis B core antigen (HbcAg) from Hepatitis B virus, a human papillomavirus LI (HPV LI) protein, a matrix protein Ml from influenza A virus, a ferritin, a riboflavin synthase, a dihydrolipoyl acetyltransferase (E2p), or a combination thereof, including their codon optimized nucleic acid sequences, fragments, mutants, variants, comparable equivalents, or functional analogs thereof.
  • HbcAg hepatitis B core antigen
  • HPV LI human papillomavirus LI
  • E2p dihydrolipoyl acetyltransferase
  • the self-assembling peptide is a ferritin comprising a ferritin subunit or a ferritin peptide, a dihydrolipoyl acetyltransferase (E2p), a lumazine synthase, an MS2 coat protein, or a combination thereof.
  • the self-assembling peptide is a ferritin comprising a ferritin subunit or a ferritin peptide, a dihydrolipoyl acetyltransferase (E2p), a lumazine synthase, an MS2 coat protein, or a combination thereof.
  • the multisubunit nucleic acid according to paragraph 34 wherein the ferritin peptide is obtained or derived from Helicobacter pylori ferritin or Listeria innocua ferritin, the lumazine synthase is obtained or derived from Aquifex aeolicus or Bacillus subtilis, the MS2 coat protein is obtained or derived from Emesvirus zinderi, and the dihydrolipoyl acetyltransferase (E2p) is obtained or derived from Bacillus stearothermophilus.
  • the ferritin peptide is obtained or derived from Helicobacter pylori ferritin or Listeria innocua ferritin
  • the lumazine synthase is obtained or derived from Aquifex aeolicus or Bacillus subtilis
  • the MS2 coat protein is obtained or derived from Emesvirus zinderi
  • the multisubunit nucleic acid according to paragraph 38 wherein the cleavage peptide is a golgi specific cleavage peptide, a self cleaving peptide, or a combination thereof.
  • the multisubunit nucleic acid according to paragraph 42 wherein the multisubunit nucleic acid further encodes a second signal peptide on the amino-terminus of all or some polypeptides of the plurality.
  • the multisubunit nucleic acid according to paragraph 48 wherein the envelope protein is obtained or derived from glycoprotein L of a herpes simplex virus 1 (HSV1).
  • the multisubunit nucleic acid according to paragraph 48 wherein the envelope protein is obtained or derived from glycoprotein N of a herpes simplex virus 1 (HSV1).
  • the multisubunit nucleic acid according to paragraph 57 wherein the glycoprotein N comprises an amino acid sequence of any one of SEQ ID NOs: 3268-3283.
  • the multisubunit nucleic acid according to paragraph 48 wherein the envelope protein is obtained or derived from glycoprotein D of a herpes simplex virus 1 (HSV1).
  • the multisubunit nucleic acid according to paragraph 67 wherein the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, glycoprotein C, glycoprotein D, glycoprotein I, glycoprotein E, or a combination thereof of a herpes simplex virus 2 (HSV2).
  • the multisubunit nucleic acid according to paragraph 68 wherein the envelope protein is obtained or derived from glycoprotein M of a herpes simplex virus 2 (HSV2).
  • CMV cytomegalovirus
  • CMV cytomegalovirus
  • CMV cytomegalovirus
  • the multisubunit nucleic acid according to paragraph 97 wherein the glycoprotein N comprises an amino acid sequence of any one of SEQ ID NOs: 3293-3327.
  • CMV cytomegalovirus
  • CMV cytomegalovirus
  • the multisubunit nucleic acid according to paragraph 105 wherein the UL130 comprises an amino acid sequence of any one of SEQ ID NOs: 17436-18255.
  • CMV cytomegalovirus
  • the multisubunit nucleic acid according to paragraph 112 wherein the envelope protein is obtained or derived from glycoprotein B of an Epstein-Barr virus (EBV).
  • the multisubunit nucleic acid according to paragraph 112 wherein the envelope protein is obtained or derived from glycoprotein L of an Epstein-Barr virus (EBV).
  • the multisubunit nucleic acid according to paragraph 112 wherein the envelope protein is obtained or derived from glycoprotein N of an Epstein-Barr virus (EBV).
  • the multisubunit nucleic acid according to paragraph 112 wherein the envelope protein is obtained or derived from glycoprotein 220 of an Epstein-Barr virus (EBV).
  • the glycoprotein B comprises an amino acid sequence of any one of SEQ ID NOs: 2624-2639; b) the glycoprotein H comprises an amino acid sequence of any one of SEQ ID NOs: 2870-2885; c) the glycoprotein L comprises an amino acid sequence of any one of SEQ ID NOs: 3038-3049. d) the glycoprotein M comprises an amino acid sequence of any one of SEQ ID NOs: 3174-3187; and e) the glycoprotein N comprises an amino acid sequence of any one of SEQ ID NOs: 3286-3292.
  • the glycoprotein B comprises an amino acid sequence of any one of SEQ ID NOs: 2738-2746; b) the glycoprotein H comprises an amino acid sequence of any one of SEQ ID NOs: 2968-2972; c) the glycoprotein L comprises an amino acid sequence of any one of SEQ ID NOs: 3104-3108; d) the glycoprotein M comprises an amino acid sequence of any one of SEQ ID NOs: 3232-3233; and e) the glycoprotein N comprises an amino acid sequence of any one of SEQ ID NOs: 3328-3229.
  • the multisubunit nucleic acid according to paragraph 46 wherein the target peptide is obtained or derived from envelope protein of a human herpesvirus 7 (HHV7).
  • the multisubunit nucleic acid according to paragraph 136 wherein: a) the glycoprotein B comprises an amino acid sequence of SEQ ID NOs: 2747; b) the glycoprotein H comprises an amino acid sequence of SEQ ID NOs: 2973; c) the glycoprotein L comprises an amino acid sequence of SEQ ID NOs: 3109; d) the glycoprotein M comprises an amino acid sequence of SEQ ID NOs: 3234; and e) the glycoprotein N comprises an amino acid sequence of SEQ ID NOs: 3330.
  • KSHV Kaposi’s sarcoma-associated herpesvirus
  • the glycoprotein B comprises an amino acid sequence of any one of SEQ ID NOs: 2784-2795; b) the glycoprotein H comprises an amino acid sequence of any one of SEQ ID NOs: 2983-2997; c) the glycoprotein L comprises an amino acid sequence of any one of SEQ ID NOs: 3124-3127; d) the glycoprotein M comprises an amino acid sequence of any one of SEQ ID NOs: 3263-3267; and e) the glycoprotein N comprises an amino acid sequence of any one of SEQ ID NOs: 3345-3349.
  • the multisubunit nucleic acid according to paragraph 147, wherein the regulatory protein is selected from the group comprising multifunctional regulatory of expression, DNA polymerase, DNA polymerase processivity subunit, helicase- primase ATPase subunit, helicase-primase RNA pol subunit B, helicase-primase subunit C, single strand DNA binding protein, alkaline deoxyribonuclease, deoxyuridine triphosphatase, uracil-DNA glycosidase, ribonucleotide reductase large subunit, ribonucleotide reductase subunit 2, EBNA1, EBNA2, EBNA3, LMP1, LMP2, maturational protease, assembly protein, capsid transport nuclear protein, terminase ATPase subunit 1, terminase DNA binding subunit 2, terminase binding protein, nuclear egress membrane protein, nuclear egress lamina protein, or a combination thereof of a herpe
  • the multisubunit nucleic acid according to paragraph 152 wherein the T cell epitope comprises an amino acid sequence of any one of SEQ ID NOs: 7753-15724.
  • a lipid nanoparticle composition comprising a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and the multisubunit nucleic acid according to any one of the preceding paragraphs.
  • the lipid nanoparticle composition according to paragraph 155 wherein the phospholipid is present in an amount from 2 mol percent to 65 mol percent.
  • a multisubunit peptide comprising two or more polypeptides, wherein some or all polypeptides comprises either a target peptide, a linker peptide, and a selfassembling peptide, or a linker peptide, a target peptide, a linker peptide, and a selfassembling peptide or a combination thereof, wherein one polypeptide is connected to another polypeptide by a cleavage peptide, wherein the multisubunit peptide includes a signal peptide on the amino-terminus of one or more of the polypeptides, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.
  • the multisubunit peptide according to paragraph 172 wherein the herpesvirus is selected from the group comprising herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), Kaposi’s sarcoma-associated herpesvirus (KSHV), or a combination thereof.
  • HSV1 herpes simplex virus 1
  • HSV2 herpes simplex virus 2
  • VZV varicella-zoster virus
  • CMV cytomegalovirus
  • HHV6 human herpesvirus 6
  • HHV7 human herpesvirus 7
  • Epstein-Barr virus EBV
  • Kaposi’s sarcoma-associated herpesvirus KSHV
  • HBsAg hepatitis B surface antigen
  • HcAg hepatitis B core antigen
  • HPV LI human papillomavirus LI
  • E2p
  • the self-assembling peptide is a ferritin comprising a ferritin subunit or a ferritin peptide, a dihydrolipoyl acetyltransferase (E2p), a lumazine synthase, an MS2 coat protein, or a combination thereof.
  • the multisubunit peptide according to paragraph 189 wherein the ferritin peptide is obtained or derived from Helicobacter pylori ferritin or Listeria innocua ferritin, the lumazine synthase is obtained or derived from Aquifex aeolicus or Bacillus subtilis, the MS2 coat protein is obtained or derived from Emesvirus zinderi, and the dihydrolipoyl acetyltransferase (E2p) obtained or derived from Bacillus stearothermophilus.
  • HSV1 herpes simplex virus 1
  • HSV2 herpes simplex virus 2
  • CMV cytomegalovirus
  • CMV cytomegalovirus
  • CMV cytomegalovirus
  • CMV cytomegalovirus
  • CMV cytomegalovirus
  • CMV cytomegalovirus
  • EBV Epstein-Barr virus
  • the multisubunit peptide according to paragraph 257 wherein the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, glycoprotein 350, glycoprotein 220, glycoprotein 42, or a combination thereof of an Epstein-Barr virus (EBV).
  • the glycoprotein B comprises an amino acid sequence of any one of SEQ ID NOs: 2748-2783.
  • the multisubunit peptide according to paragraph 261 wherein the glycoprotein H comprises an amino acid sequence of any one of SEQ ID NOs: 2974-2982.

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Abstract

La présente divulgation concerne de manière générale des acides nucléiques à sous-unités multiples comprenant une pluralité de séquences polynucléotidiques, chaque séquence polynucléotidique de la pluralité comprenant une séquence cible, une séquence de liaison et une séquence d'autoassemblage, ou une séquence de liaison, une séquence cible, une séquence de liaison et une séquence d'autoassemblage, ou une combinaison de celles-ci, chaque séquence polynucléotidique de la pluralité étant reliée à une séquence polynucléotidique adjacente de la pluralité par une séquence de clivage, et l'acide nucléique à sous-unités multiples comprenant en outre une séquence de signal en amont d'une ou de plusieurs des séquences polynucléotidiques de la pluralité, la séquence cible étant obtenue ou dérivée à partir d'un herpèsvirus. L'acide nucléique à sous-unités multiples code pour un peptide à sous-unités multiples.
PCT/IB2025/000388 2024-06-27 2025-06-25 Vaccins à base d'herpèsvirus à sous-unités multiples et agents thérapeutiques Pending WO2026003586A2 (fr)

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