EP1109575A2 - Lebendige virusimpfstoffe um primaten gegen hiv-1 infektion und krankheit zu beschützen - Google Patents

Lebendige virusimpfstoffe um primaten gegen hiv-1 infektion und krankheit zu beschützen

Info

Publication number: EP1109575A2
Authority: EP; European Patent Office
Prior art keywords: virus; hiv; shiv; infection; cells
Prior art date: 1998-09-29
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Withdrawn

Application number

EP99949907A

Other languages

English (en)

French (fr)

Inventor

Opendra Narayan

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.)

University of Kansas Medical Center

Original Assignee

University of Kansas Medical Center

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1998-09-29

Filing date

1999-09-28

Publication date

2001-06-27

1999-09-28 Application filed by University of Kansas Medical Center filed Critical University of Kansas Medical Center

2001-06-27 Publication of EP1109575A2 publication Critical patent/EP1109575A2/de

Status Withdrawn legal-status Critical Current

Links

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Classifications

- 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
- A61K39/21—Retroviridae, e.g. equine infectious anemia virus
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- 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
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
- 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
- A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
- A61K2039/541—Mucosal route
- 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
- A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
- A61K2039/541—Mucosal route
- A61K2039/542—Mucosal route oral/gastrointestinal
- 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
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
- 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
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/15011—Lentivirus, not HIV, e.g. FIV, SIV
- C12N2740/15034—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
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/16011—Human Immunodeficiency Virus, HIV
- C12N2740/16034—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Definitions

the present invention teaches an avirulent HIV-1 virus, wherein the vpu gene of the HIV-1 virus has been rendered non-functional or deleted.
the HIV-1 virus may have a non-functional or deleted nef gene.
the instant invention also encompasses a HIV-1 /HIV-2 chimeric virus wherein the chimeric DNA comprises HIV-2 LTR, gag, pol, and nef ' genes and HIV-1 env, tat, rev, vpu genes, where said vpu gene is rendered non-functional or is deleted.
the nef gene is optionally rendered non-functional or deleted.
SIV mac which is closely related to HIV-2 and SIVsm, causes AIDS in macaques and has been extensively used in vaccine studies. Macaques vaccinated with attenuated strains of SIV mac , produced by deleting auxiliary genes, particularly nef, resisted infection after challenge with virulent strains of SIVmac (Daniel, M. D., Kirchhoff, F., Czajak, S. C, Sehgal, P. K. & Desrosiers, R. C. Science 258, 1938-1941 (1992); Almond, N., Kent, K., Cranage, M., Rud, E., Clarke, B. & Stott, E. J.
SHIV-4 Construction of Avpu nef SHIV-4 .
the original SHIV-4 DNA consisted of 2 plasmids with the 5 ' and 3 ' regions, respectively. All manipulations were performed with the p3 ' SHIV-4.
plasmid pUC19 was digested with Sspl, blunt-ended by Klenow fragment of DNA polymerase and ligated to generate pDS.
the Sphl-Kpnl fragment (nt 6450 to 6985) of p3 ' SHIV-4 was subcloned into pDS to generate pDSvpu.
Plasma obtained from the femoral vein was centrifuged to separate plasma and buffy coats. Plasma was assayed for p27 using a capture ELISA kit (Coulter Laboratories, Hialeah, FL), and for infectivity in C8166 cells. Peripheral blood mononuclear cells (PBMC) were separated from buffy coats by centrifugation through a Ficoll-Paque (Pharmacia) density gradient.
PBMC Peripheral blood mononuclear cells
Week -7 to -1 were after Cornea inoculation; Week 1 to 4 after Intra-dermal inoculation.
SIVpolC (5'ACCAATCCATACAACACC3') (SEQ ID NO:7) and SIVpolD (5'CTGCCCAATTTAATACTCC3') (SEQ ID NO:8) 3 mM MgCl 2 and 1.25 U of Taq enzyme (Sigma, St. Louis, MO.), and a further 35 cycles were performed with the following thermal profile: 97°C for 1 minute, 55°C for 2 minutes and 72°C for 5 minutes, 1 cycle 94°C for 30 seconds, 55°C for 30 seconds, 72°C for 45 seconds, with an additional extension/cycle, 33 cycles: 94°C for 30 seconds, 55°C for 30 seconds, and 72°C for 6 minutes.
the vpu that was amplified is indicated as C (challenge vims [SH1V KLM ] or V (vaccine vims). Both challenge and vaccine vims sequences were amplified from Pna
Four of these six vaccinated macaques resisted productive infection and disease following intravaginal challenge with SHIV KLM ( ⁇ 2 test, P 0.102).
V-II virus DNA and C-virus DNA Comparison of these sequences with those of V-II virus DNA and C-virus DNA showed that the newly isolated viruses have scattered mutations in gp ⁇ 2Q and nef.
the viruses isolated from PEy and PW1 in the V-II group are variants of V-II virus, and the agent isolated from 8124 is a variant of C-virus (data not shown). There was no evidence of recombination between V- and C-virus DNAs in any of the three newly derived agents.
CD4 + T cells were equally responsive to viral antigens and CTLs recognized epitopes in all three of the structural proteins of the virus and in autologous CD4 + T cells infected with C-virus (Table 18). Although the study on CMI responses was not initiated until approximately 40 weeks post-challenge, this immune response was already in place in animals in both groups when, in the V-II group, not only had infectious virus been eliminated, but viral DNA was in the process of being eliminated in most of the animals. This contrasted with the V-I group in which infectious C-virus persisted.

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Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Virology (AREA)
General Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
Communicable Diseases (AREA)
Microbiology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Mycology (AREA)
Organic Chemistry (AREA)
Epidemiology (AREA)
General Chemical & Material Sciences (AREA)
Immunology (AREA)
Oncology (AREA)
Chemical Kinetics & Catalysis (AREA)
Molecular Biology (AREA)
Tropical Medicine & Parasitology (AREA)
AIDS & HIV (AREA)
Hematology (AREA)
Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)

EP99949907A 1998-09-29 1999-09-28 Lebendige virusimpfstoffe um primaten gegen hiv-1 infektion und krankheit zu beschützen Withdrawn EP1109575A2 (de)

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US10214398P	1998-09-29	1998-09-29
US102143P		1998-09-29
PCT/US1999/022349 WO2000018430A2 (en)	1998-09-29	1999-09-28	Live virus vaccines to protect primates from hiv-1 infection and disease

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EP (1)	EP1109575A2 (de)
AU (1)	AU6268199A (de)
CA (1)	CA2345959A1 (de)
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