EP4683661A2 - Anti-medin-immuntherapie für vaskuläre alterung und verwandten demenzen - Google Patents

Anti-medin-immuntherapie für vaskuläre alterung und verwandten demenzen

Info

Publication number
EP4683661A2
EP4683661A2 EP24775746.1A EP24775746A EP4683661A2 EP 4683661 A2 EP4683661 A2 EP 4683661A2 EP 24775746 A EP24775746 A EP 24775746A EP 4683661 A2 EP4683661 A2 EP 4683661A2
Authority
EP
European Patent Office
Prior art keywords
peptide
medin
modified
seq
fragment
Prior art date
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.)
Pending
Application number
EP24775746.1A
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English (en)
French (fr)
Inventor
Raymond Migrino
Ming Li
Jillian MADINE
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 Liverpool
US Department of Veterans Affairs
Original Assignee
University of Liverpool
US Department of Veterans Affairs
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.)
Filing date
Publication date
Application filed by University of Liverpool, US Department of Veterans Affairs filed Critical University of Liverpool
Publication of EP4683661A2 publication Critical patent/EP4683661A2/de
Pending legal-status Critical Current

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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
    • A61K39/0005—Vertebrate antigens
    • A61K39/0007—Nervous system antigens; Prions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4711—Alzheimer's disease; Amyloid plaque core protein
    • 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
    • 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
    • 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
    • A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
    • 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
    • A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
    • A61K2039/575—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2 humoral response
    • 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
    • A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
    • A61K2039/6031—Proteins
    • A61K2039/6081—Albumin; Keyhole limpet haemocyanin [KLH]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/31—Fusion polypeptide fusions, other than Fc, for prolonged plasma life, e.g. albumin

Definitions

  • AD cardio-cerebrovascular diseases
  • ADRD AD-related dementias
  • VaD vascular dementia
  • compositions and methods for reducing or disrupting medin toxicity and treating or ameliorating symptoms of vascular disease and neurodegeneration are also needed. Also needed are compositions and methods for attenuating medin-induced vascular dysfunction or neurovascular pathology as well as modulating medin aggregation.
  • compositions and methods for reducing or disrupting medin toxicity and treating or ameliorating symptoms of vascular disease and neurodegeneration are also described herein. Also described herein are compositions and methods for attenuating medin-induced vascular dysfunction or neurovascular pathology as well as modulating medin aggregation.
  • peptides comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • peptides comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form, wherein the carrier epitope is at the N terminus of the peptide.
  • peptides comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form, wherein the modified medin peptide is at the C-terminus of the peptide.
  • peptides comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form, wherein the modified medin peptide or fragment thereof is 12-18 amino acids long.
  • peptides comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of TQGARDFGHIQYVA (SEQ ID NO: 4) or TQGARNFGSVQFVA (SEQ ID NO: 3).
  • peptides comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form, wherein amino acids T at position 1 and F at position 7 of SEQ ID NO: 3 are in the D-form or wherein amino acids T at position 1 and F at position 7 of SEQ ID NO: 4 are in the D-form
  • peptides comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of LGSSKEVTGIITQGARNFGSVQFVA (SEQ ID NO: 5) or LGTQRQVTGIITQGARDFGHIQYVA (SEQ ID NO: 6).
  • peptides comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of TGIITQGARNFGSVQFVA (SEQ ID NO: 7) or TGIITQGARDFGHIQYVA (SEQ ID NO: 8).
  • peptides comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of LGTQRQVTGIITQGARDFGHIQYVA (SEQ ID NO: 6).
  • peptides comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of TGIITQGARDFGHIQYVA (SEQ ID NO: 8).
  • peptides comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form, wherein the carrier epitope is KLH.
  • nucleic acid molecules capable of encoding the peptides disclosed herein. Also disclosed herein are nucleic acid molecules capable of encoding a peptide comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • vectors comprising one or more of the nucleic acid molecules disclosed herein.
  • vectors comprising a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • cells comprising one or more of the peptides, nucleic acid molecules or vectors disclosed herein.
  • the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • cells comprising a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • cells comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • compositions comprising one or more of the peptides, nucleic acid constructs, vectors or cells disclosed herein.
  • compositions comprising a peptide comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • compositions comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • compositions comprising a vector comprising a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • compositions comprising a cell, wherein the cell comprises a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • compositions comprising one or more of the peptides, nucleic acid constructs, vectors, cells or compositions disclosed herein.
  • compositions comprising a peptide comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and a pharmaceutically acceptable carrier.
  • compositions comprising a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and a pharmaceutically acceptable carrier.
  • compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a earner epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and a pharmaceutically acceptable carrier.
  • compositions comprising a cell, wherein the cell comprises a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and a pharmaceutically acceptable carrier.
  • compositions comprising a composition, wherein the composition comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and a pharmaceutically acceptable carrier.
  • Disclosed herein are methods of disrupting medin toxicity in a subject in need thereof comprising administering an effective amount of one or more of the peptides, nucleic acid constructs, vectors, cells, compositions or pharmaceutical compositions disclosed herein. [0035] Disclosed herein are methods of reversing medin induced endothelial activation in a subject in need thereof comprising administering an effective amount of one or more of the peptides, nucleic acid constructs, vectors, cells, compositions or pharmaceutical compositions disclosed herein.
  • Disclosed herein are methods of inducing an immune response in a subject in need thereof comprising administering an effective amount of one or more of the peptides, nucleic acid constructs, vectors, cells, compositions or pharmaceutical compositions disclosed herein. [0037] Disclosed herein are methods of vaccinating a subject in need thereof comprising administering an effective amount of one or more of the peptides, nucleic acid constructs, vectors, cells, compositions or pharmaceutical compositions disclosed herein.
  • Disclosed herein are methods of modulating vascular disease in a subject in need thereof comprising administering an effective amount of one or more of the peptides, nucleic acid constructs, vectors, cells, compositions or pharmaceutical compositions disclosed herein.
  • methods of modulating medin aggregation in a subject in need thereof comprising administering an effective amount of one or more of the peptides, nucleic acid constructs, vectors, cells, compositions or pharmaceutical compositions disclosed herein.
  • IL-8 interleukin
  • ICM-1 intercellular adhesion molecule-1
  • PAI-1 plasminogen activator inhibitor-1
  • Disclosed herein are methods of modulating or preventing cerebrovascular dysfunction, cognitive dysfunction, neurodegeneration and/or neurovascular pathology in a subject in need thereof comprising administering an effective amount of one or more of the peptides, nucleic acid constructs, vectors, cells, compositions or pharmaceutical compositions disclosed herein.
  • Disclosed herein are methods of modulating or preventing amyloid plaque formation in a subject in need thereof comprising administering an effective amount of one or more of the peptides, nucleic acid constructs, vectors, cells, compositions or pharmaceutical compositions disclosed herein.
  • Disclosed herein are methods of reducing the rate of grow th of amyloid plaques in a subject in need thereof comprising administering an effective amount of one or more of the peptides, nucleic acid constructs, vectors, cells, compositions or pharmaceutical compositions disclosed herein.
  • Disclosed herein are methods of treating coronary artery disease and/or ischemic heart disease in a subject in need thereof comprising administering an effective amount of one or more of the peptides, nucleic acid constructs, vectors, cells, compositions or pharmaceutical compositions disclosed herein.
  • FIG. 1 describes a scheme for inhibiting medin-induced toxicity .
  • FIGs. 2A-2F shows that cerebrovascular medin is higher in AD.
  • FIG. 2A shows medin deposits (brown DAB) in elderly brain artenoles.
  • FIG. 2B shows higher arteriole medin score in AD versus non-demented (ND) donors.
  • FIG. 2C shows higher arteriole medin seen in donors with more neurofibrillary' tangles (Braak stage) and higher Ap plaque density 7 score (FIG. 2D).
  • FIG. 2E shows AUC-ROC analysis shows arteriole medin and cerebral amyloid angiopathy (CAA), but not circle of Willis (CoW) atherosclerosis score, are highly predictive of AD diagnosis.
  • FIG. 2F shows that among vascular pathologies, arteriole medin has the highest odds ratio for AD diagnosis.
  • FIGs. 3A-3E show medin causes cerebrovascular dy sfunction in aging wild-ty pe mice.
  • FIG. 3 A shows schematic structure of human and C57BL/6J mouse Mfge8 gene showing major protein domains including medin component (left), amino acid sequence comparison of human medin with homologous mouse sequence and TANGO prediction of aggregation-prone peptides within the medin sequence with high conservation but lower aggregation propensity in mouse (right).
  • FIG. 3B shows that in aged (20 month old) but not young (2 month old) mice, medin aggregate-like structures are present in brain vasculature (white arrows) and directly correlate with age (FIG. 3C).
  • Medin knockout FIG.
  • FIGs. 4A-4L show that medin induces endothelial dysfunction, oxidative stress and inflammatory’ activation.
  • FIG. 4A shows ex-vivo human collateral cerebral arteries exposed to medin (5 pM, 1 hour) show impaired dilator response to acetylcholine (endothelial dysfunction).
  • FIGs. 4A shows ex-vivo human collateral cerebral arteries exposed to medin (5 pM, 1 hour) show impaired dilator response to acetylcholine (endothelial dysfunction).
  • FIGs. 4E-4I show in human endothelial cells. 20 hr. medin exposure increased activated NFKB with increased pro-inflammatory activation as seen with increased IL-8, IL-6, ICAM-1 and PALL These changes were reversed by NFKB inhibitor (data not shown).
  • FIGs. 4J-4L show' 3D chip with astrocytes in central (green) chamber and either ECs or no ECs in side chambers (red). Astrocyte production of IL-8 was higher when ECs are present following exposure to medin, suggesting paracrine-type modulation of glial inflammation by endothelial activation induced by medin.
  • FIG. 5 is a picture of a western blot using primary’ monoclonal antibodies purified from C57BL/6 mice immunized with KLH-C-T’-QGARD-F'-GHIQYVA (medin fragment): the Western blot showed that the mAb following immunization had great ability to attach/conjugate with medin fragment (lane 5), purified recombinant human medin (lane 2) and medin polypeptides in human umbilical vein endothelial cells (lane 3).
  • FIGs. 6A-6B show ICAM-1 (FIG. 6A) or VCAM-1 (FIG. 6B) gene expression in human brain endothelial cells in vitro when mixed with medin and monoclonal antibodies extracted from C57BL/6 mice immunized with KLH-C-T’-QGARD-F’-GHIQYVA (medin fragment). This shows that following immunization with KLH-C-T’-QGARD-F’- GHIQYVA, the resulting monoclonal antibody produced showed ability 7 to suppress endothelial activation and inflammation in endothelial cells induced by medin.
  • FIGs. 7A-B shows that medin is present in cerebral artery of 12 month (FIG. 7B) but not 2 month old (FIG. 7A) SAMP8 mouse (using anti-medin antibody).
  • SAMP8 is a mouse model of premature aging.
  • FIG. 8 shows a schematic showing the experimental design for medin vaccine efficacy testing.
  • FIGs. 9A-9D show medin in coronary arteries following post-mortem histology of elderly brain and body donors.
  • FIG. 9A show coronary 7 artery 7 from donor who had myocardial infarction (MI) and diabetes and tissue did not receive anti-medin primary 7 antibody, thus serving as tissue control.
  • FIGs. 9B-C show coronary arteries from donors who had MI and diabetes and stained with anti-medin primary antibody (DAB staining); blue/brown/black stain (sample regions in black arrows) denotes medin which is found in tunica intima (endothelial layer), tunica media (smooth muscle layer) and tunica adventitia of the coronary arteries.
  • DAB staining anti-medin primary antibody
  • blue/brown/black stain denotes medin which is found in tunica intima (endothelial layer), tunica media (smooth muscle layer) and tunica adventitia of the coronary arteries.
  • FIG. 9D shows prominent medin accumulation in endothelial cells and in smooth muscle layer of coronary 7 artery of a diabetic patient. The figure indicates that coronary 7 artery disease is accompanied by coronary arterial medin deposit! on/accumulati on.
  • FIGs. 10A-10B show effects of polyclonal antibodies against medin derived from medin immunization.
  • FIG. 10A shows that following immunization of rabbits with human medin, polyclonal antibodies targeting three epitopes of medin were created.
  • FIG. 10B shows that when human endothelial cells were treated with medin, there was increased pro- inflammatory 7 gene expression (IL-8 (left), IL-6 (center) and IL- 1 [3 (right)), and the pro- inflammatory 7 effect of medin was reduced when medin was co-treated with polyclonal antibodies derived from medin vaccination of rabbits.
  • IL-8 left
  • IL-6 center
  • IL- 1 [3 (right) pro- inflammatory 7 effect of medin was reduced when medin was co-treated with polyclonal antibodies derived from medin vaccination of rabbits.
  • Ranges may be expressed herein as from “about” one particular value, and/or to “about” another particular value.
  • the term “about” is used herein to mean approximately, in the region of, roughly, or around. When the term “about” is used in conjunction with a numerical range, it modifies that range by extending the boundaries above and below the numerical values set forth. In general, the term “about” is used herein to modify a numerical value above and below the stated value by a variance of 20%. When such a range is expressed, another embodiment includes from the one particular value and/or to the other particular value.
  • amino acid sequence refers to a list of abbreviations, letters, characters or words representing amino acid residues.
  • the amino acid abbreviations used herein are conventional one letter codes for the amino acids and are expressed as follows: A. alanine; C, cysteine; D aspartic acid; E, glutamic acid; F, phenylalanine; G, glycine; H histidine; I isoleucine; K. lysine; L, leucine; M, methionine; N, asparagine; P.
  • proline glutamine
  • R arginine
  • S serine
  • T threonine
  • V valine
  • W tryptophan
  • Y tyrosine.
  • All alpha amino acids except glycine can exist in either of two enantiomers, called L-amino acids or D-amino acids, which are mirror images of each other.
  • amino acid refers to an organic molecule with a basic amino group (-NH2), an acidic carboxyl group (-COOH), a proton and a variable ‘R’ group bound to an sp3 hybridized central carbon atom.
  • the N-terminus of a peptide has a free amino group (-NH2).
  • the C-terminus of a peptide has a free carboxyl group (-COOH).
  • D-amino acid or “amino acid in the D-form” refer to amino acids where the stereogenic carbon alpha to the amino group has the D-configuration.
  • a “D-amino acid” is the enantiomer of an amino acid that is capable of rotating plane polarized light clockwise (right-hand side). D-amino acids are designated with the prime (’) symbol.
  • L-amino acid or “amino acid in the L-form” refer to amino acids where the stereogenic carbon alpha to the amino group has the L-configuration.
  • L amino acid is the enantiomer of an amino acid that is capable of rotating plane polarized light anticlockwise (left-hand side). With the exception of achiral glycine, natural amino acids have the L configuration.
  • Peptide refers to any peptide, oligopeptide, polypeptide, gene product, expression product, or protein.
  • a peptide is comprised of consecutive amino acids.
  • the term “peptide” encompasses naturally occurring or synthetic molecules.
  • a residue of a peptide is an amino acid. As used herein if an amino acid is said to be in the 5 th position, it is the 5 th amino acid from the N-terminus of the peptide.
  • fragment is meant a portion of a polypeptide or nucleic acid molecule, such as, but not limited to, a truncation mutant. This portion contains, preferably, at least about 5%, 10%. 20%. 30%. 40%. 50%. 60%. 70%. 80%. 90%. 95% of the entire length of the reference nucleic acid molecule or polypeptide.
  • a fragment of a polypeptide may contain about 5, about 10, about 15, about 20, about 25 or about 30 or more amino acids.
  • a fragment of a polypeptide may contain about 1000, about 1500, about 2000, about 2500 or about 3000 or more amino acids.
  • epitopope refers to a localized region on the surface of an antigen capable of eliciting an immune response.
  • carrier epitope refers to an inactive, accessory substance used as a vehicle to deliver a vaccine to a subject.
  • Non-limiting examples of carrier epitopes include KLH, N19 poly epitope, CRM 197. diphtheria toxoid (DT), tetanus toxoid (TT). Haemophilus protein D (PD), the outer membrane protein complex of serogroup B meningococcus (OMPC), BSA (bovine serum albumin) , OVA (ovalbumin), beta glucosidase and haptens.
  • KLH refers to keyhole limpet hemocyanin (“KLH”) which is a large, multisubunit, oxygen-carrying, metalloprotein that is found in the hemolymph of the giant keyhole limpet, Megathura crenulata.
  • KLH is an effective carrier protein for several reasons. Its large size and numerous epitopes generate a substantial immune response, and abundance of lysine residues for coupling haptens allows a high hapten: carrier protein ratio, increasing the likelihood of generating hapten-specific antibodies.
  • KLH may also refer to a fragment of KLH.
  • sample is meant to mean an animal; a tissue or organ from an animal: a cell (either within a subject, taken directly from a subject, or a cell maintained in culture or from a cultured cell line); a cell lysate (or lysate fraction) or cell extract; or a solution containing one or more molecules derived from a cell or cellular material (e.g. a polypeptide or nucleic acid), which is assayed as described herein.
  • a sample may also be any body fluid or excretion (for example, but not limited to, blood, urine, stool, saliva, tears, bile) that contains cells or cell components.
  • subject refers to the target of administration, e.g. an animal.
  • the subject of the disclosed methods can be a vertebrate, such as a mammal.
  • the subject can be a human.
  • the term does not denote a particular age or sex.
  • Subject can be used interchangeably with “individual” or “patient”.
  • isolated polypeptide or “purified polypeptide” is meant to mean a polypeptide (or a fragment thereof) that is substantially free from the materials with which the polypeptide is normally associated in nature.
  • the polypeptides of the invention, or fragments thereof can be obtained, for example, by extraction from a natural source (for example, a mammalian cell), by expression of a recombinant nucleic acid encoding the polypeptide (for example, in a cell or in a cell-free translation system), or by chemically synthesizing the polypeptide.
  • polypeptide fragments may be obtained by any of these methods, or by cleaving full length proteins and/or polypeptides.
  • Dose or “dosage” as used herein refers to a specific quantity 7 of a therapeutic agent, such as a peptide, that is taken at specific times.
  • treat is meant to mean administer one of the disclosed compositions to a subject, such as a human or other mammal (for example, an animal model), that has atherosclerosis, in order to prevent or delay a worsening of the effects of the disease or condition, or to partially or fully reverse the effects of the disease.
  • a subject such as a human or other mammal (for example, an animal model), that has atherosclerosis, in order to prevent or delay a worsening of the effects of the disease or condition, or to partially or fully reverse the effects of the disease.
  • prevent is meant to mean minimize the chance that a subject will develop medin toxicity, medin-induced endothelial activation, medin -induced vascular dysfunction, medin-induced neurovascular pathology, vascular disease, medin aggregation, vascular dysfunction, inflammation, cerebrovascular dysfunction, cognitive dysfunction, neurodegeneration, neurovascular pathology, amyloid plaque formation, coronary artery disease and/or ischemic heart disease.
  • treatment cycle refers to the administration of a peptide for an established period of time.
  • a treatment cycle includes a wide range of dosages of peptide as well as different lengths of time for administering one or more ofthe peptides, nucleic acid constructs, vectors, cells, compositions or pharmaceutical compositions disclosed herein.
  • a treatment cycle can be a three month period wherein one of the peptides disclosed herein is administered twice a week for the three month period.
  • an effective amount is meant to mean a sufficient amount of one or more of the peptides, nucleic acid constructs, vectors, cells, compositions or pharmaceutical compositions disclosed herein to provide the desired effect.
  • an effective amount of one or more of the peptides, nucleic acid constructs, vectors, cells, compositions or pharmaceutical compositions disclosed herein can be an amount that provides a therapeutic affect and provides sustained therapeutic effects after withdrawal of the treatment.
  • An effective amount of one or more of the peptides, nucleic acid constructs, vectors, cells, compositions or pharmaceutical compositions disclosed herein can be an amount that is able to cause a benefit illustrated by a disruption or decrease in medin toxicity, a reversal of medin-induced endothelial activation, an induction of an immune response, a modulation, reduction or prevention of vascular disease, a modulation, reduction or prevention of medin aggregation, treating, reducing or preventing vascular dysfunction or inflammation, reducing interleukin (IL)-8, IL-6, intercellular adhesion molecule-1 (ICAM-1) and/or plasminogen activator inhibitor-1 (PAI-1), modulating, reducing or preventing amyloid plaque formation, reducing the rate of growth of amyloid plaques, as well as an amount that allows for a sustained therapeutic effect after withdrawal of the peptide, nucleic acid molecule, vector, cell, composition or pharmaceutical composition.
  • IL interleukin
  • IAM-1 intercellular adh
  • an appropriate “effective amount” may be determined by one of ordinary skill in the art using only routine experimentation.
  • sustained therapeutic effect is a therapeutic effect that persists after the therapeutic has been withdrawn. For example, the sustained therapeutic effect is maintained even after the acute disruption in medin toxicity 7 is gone.
  • nucleic acid refers to a naturally occurring or synthetic oligonucleotide or polynucleotide, whether DNA or RNA or DNA-RNA hybrid, singlestranded or double-stranded, sense or antisense, which is capable of hybridization to a complementary nucleic acid by Watson-Crick base-pairing.
  • Nucleic acids of the invention can also include nucleotide analogs (e.g., BrdU), and non-phosphodiester intemucleoside linkages (e g., peptide nucleic acid (PNA) or thiodiester linkages).
  • nucleic acids can include, without limitation, DNA, RNA, cDNA, gDNA, ssDNA, dsDNA or any combination thereof.
  • vector refers to a nucleic acid sequence capable of transporting into a cell another nucleic acid to which the vector sequence has been linked.
  • expression vector includes any vector, (e.g., a plasmid, cosmid or phage chromosome) containing a gene construct in a form suitable for expression by a cell (e.g., linked to a transcriptional control element).
  • Plasmid and “vector” are used interchangeably, as a plasmid is a commonly used form of vector.
  • the invention is intended to include other vectors which serve equivalent functions.
  • expression vector is herein to refer to vectors that are capable of directing the expression of genes to which they are operatively-linked. Common expression vectors of utility in recombinant DNA techniques are often in the form of plasmids.
  • Recombinant expression vectors can comprise a nucleic acid as disclosed herein in a form suitable for expression of the acid in a host cell.
  • the recombinant expression vectors can include one or more regulatory elements or promoters, which can be selected based on the host cells used for expression that is operatively linked to the nucleic acid sequence to be expressed.
  • disrupting medin toxicity means a decrease or reduction in any medin-mediated effect on a subject, including, but not limited to, medin-induced endothelial actiation, medin-induced vascular dysfunction or vascular disease, medin-induced neurovascular pathology, medin-induced inflammation, medin-induced modulation of IL-8, IL-6, ICAM-1 and/or PAI-1, medin-induced cerebrovascular dysfunction, medin-induced cognitive dysfunction, medin-induced neurodegeneration, medin-induced neurovascular pathology', medin-induced amyloid plaque formation, medin-induced coronary artery' disease and/or medin-induced ischemic heart disease.
  • Non-limiting examples of the peptides of the disclosure are provided herein. Disclosed herein are peptides comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide.
  • peptides comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • the fragment of SEQ ID NO: 1 can be SEQ ID NO: 3, SEQ ID NO:
  • SEQ ID NO: 29 SEQ ID NO: 29, SEQ ID NO: 31, SEQ ID NO: 33, SEQ ID NO: 35, SEQ ID NO: 37 or SEQ ID NO: 39.
  • the fragment of SEQ ID NO: 2 can be SEQ ID NO: 4, SEQ ID NO:
  • SEQ ID NO: 30 SEQ ID NO: 32, SEQ ID NO: 34, SEQ ID NO: 36, SEQ ID NO: 38 or SEQ ID NO:40.
  • no more than 7 consecutive amino acids of the modified medin peptide or fragment thereof are in the L-form. In some aspects, no more than 6 consecutive amino acids of the modified medin peptide or fragment thereof are in the L-form. In some aspects, no more than 5 consecutive amino acids of the modified medin peptide or fragment thereof are in the L-form. In some aspects, no more than 4 consecutive amino acids of the modified medin peptide or fragment thereof are in the L-form.
  • the modified medin peptide or fragment thereof has at least one amino acid in the D-form. In some aspects, the modified medin peptide or fragment thereof has at least two amino acids in the D-form. In some aspects, the modified medin peptide or fragment thereof has at least three amino acids in the D-form. In some aspects, the modified medin peptide or fragment thereof has at least four amino acids in the D-form. In some aspects, the modified medin peptide or fragment thereof has at least five amino acids in the D-form. In some aspects, the modified medin peptide or fragment thereof has at least six amino acids in the D-form. In some aspects, the modified medin peptide or fragment thereof has at least seven amino acids in the D-form.
  • the modified medin peptide or fragment thereof has at least eight amino acids in the D-form. In some aspects, the modified medin peptide or fragment thereof has at least nine amino acids in the D-form. In some aspects, the modified medin peptide or fragment thereof has at least ten amino acids in the D- form.
  • the modified medin peptide is SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64.
  • SEQ ID NO: 65 SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77 or SEQ ID NO: 78.
  • the carrier epitope is at the N terminus of a peptide. In some aspects, the carrier epitope is at the C-terminus of a peptide.
  • the modified medin peptide or fragment thereof is at the C-terminus of the peptide. In some aspects, the modified medin peptide or fragment thereof is at the N- terminus of the peptide.
  • the modified medin peptide or fragment thereof is from 10 to 25 amino acids long. In some aspects, the modified medin peptide or fragment thereof is from 12 to 18 amino acids long. In some aspects, the modified medin peptide or fragment thereof is 10 amino acids long. In some aspects, the modified medin peptide or fragment thereof is 11 amino acids long. In some aspects, the modified medin peptide or fragment thereof is 12 amino acids long. In some aspects, the modified medin peptide or fragment thereof is 13 amino acids long. In some aspects, the modified medin peptide or fragment thereof is 14 amino acids long. In some aspects, the modified medin peptide or fragment thereof is 15 amino acids long. In some aspects, the modified medin peptide or fragment thereof is 16 amino acids long.
  • the modified medin peptide or fragment thereof is 17 amino acids long. In some aspects, the modified medin peptide or fragment thereof is 18 amino acids long. In some aspects, the modified medin peptide or fragment thereof is 19 amino acids long. In some aspects, the modified medin peptide or fragment thereof is 20 amino acids long. In some aspects, the modified medin peptide or fragment thereof is 21 amino acids long. In some aspects, the modified medin peptide or fragment thereof is 22 amino acids long. In some aspects, the modified medin peptide or fragment thereof is 23 amino acids long. In some aspects, the modified medin peptide or fragment thereof is 24 amino acids long. In some aspects, the modified medin peptide or fragment thereof is 25 amino acids long.
  • the disclosed peptides can be made synthetically or recombinantly.
  • the disclosed peptides can be conjugated to a carrier protein (e.g. conjugated to KLH using methods such as maleimide method).
  • contemplated are peptides which do not comprise the C-terminal amino acid (Alanine; A) of SEQ ID NO: 1 or SEQ ID NO: 2.
  • peptides which do not comprise the last fifteen amino acids of SEQ ID NO: 1 or SEQ ID NO: 2.
  • petides comprising any of the sequences of SEQ ID NO: 1 through SEQ ID NO. 78.
  • variants or derivatives of the peptides disclosed herein are also disclosed.
  • Nonlimiting examples of the peptides have been described herein (see Tables 1-2, for example).
  • the term “analog” is used interchangeably with “variant” and “derivative.”
  • Variants and derivatives are well understood to those of skill in the art and can involve amino acid sequence modifications. Such amino acid sequence modifications typically fall into one or more of three classes: substantial; insertional; or deletional variants. Insertions include amino and/or carboxyl terminal fusions as well as intrasequence insertions of single or multiple amino acid residues.
  • Insertions ordinarily are smaller insertions than those of amino or carboxyl terminal fusions, for example, on the order of one to four residues.
  • These variants ordinarily are prepared by site-specific mutagenesis of nucleotides in the DNA encoding the protein, thereby producing DNA encoding the variant, and thereafter expressing the DNA in recombinant cell culture.
  • Techniques for making substitution mutations at predetermined sites in DNA having a known sequence are well known, for example Ml 3 primer mutagenesis and PCR mutagenesis.
  • Amino acid substitutions are typically of single residues, but can occur at a number of different locations at once.
  • Substitutions, deletions, insertions or any combination thereof may be combined to arrive at a final derivative or analog.
  • Substitutional variants are those in which at least one residue has been removed and a different residue inserted in its place. Such substitutions generally are made in accordance with Tables 3 and 4 and are referred to as conservative substitutions.
  • Substantial changes in function or immunological identity are made by selecting substitutions that are less conservative than those in Table 3, i.e., selecting residues that differ more significantly in their effect on maintaining (a) the structure of the polypeptide backbone in the area of the substitution, for example as a sheet or helical conformation, (b) the charge or hydrophobicity of the molecule at the target site, or (c) the bulk of the side chain.
  • substitutions which in general are expected to produce the greatest changes in the protein properties are those in which: (a) the hydrophilic residue, e.g.
  • seryl or threonyl is substituted for (or by) a hydrophobic residue, e.g., leucyl, isoleucyl, phenylalanyl, valyl or alanyl; Tryptophan, Tyrosinyl (b) a cysteine or proline is substituted for (or by) any other residue; (c) a residue having an electropositive side chain, e.g., lysyl, arginyl, or hystidyl, is substituted for (or by) an electronegative residue, e.g.
  • variants and derivatives of the disclosed proteins herein are to define them in terms of homology/identity to specific known sequences.
  • variants of peptides herein disclosed which have at least, 70% or at least 75% or at least 80% or at least 85% or at least 90% or at least 95% or at least 96% or at least 97% or at least 98% or at least 99% identity to the peptides specifically recited herein.
  • Those of skill in the art readily understand how to determine the identity of two proteins.
  • the polypeptides can be modified by either natural processes, such as post- translational processing, or by chemical modification techniques which are well known in the art.
  • Modifications can occur anywhere in the polypeptide, including the peptide backbone, the amino acid side-chains and the amino or carboxyl termini.
  • the same type of modification can be present in the same or varying degrees at several sites in a given polypeptide.
  • a given polypeptide can have many types of modifications.
  • Modifications include, without limitation, acetylation, acylation, ADP-ribosylation, amidation, covalent cross-linking or cyclization, covalent attachment of flavin, covalent attachment of a heme moiety, covalent attachment of a nucleotide or nucleotide derivative, covalent attachment of a lipid or lipid derivative, covalent attachment of a phosphytidylinositol, disulfide bond formation, demethylation, formation of cysteine or pyroglutamate, fonnylation, gamma-carboxylation, glycosylation, GPI anchor formation, hydroxylation, iodination, methylation, myristolyation, oxidation, pegylation, proteolytic processing, phosphorylation, prenylation, racemization, selenoylation, sulfation, and transfer-RNA mediated addition of amino acids to protein such as arginylation.
  • nucleic acids that can encode those polypeptide sequences are also disclosed. This would include all degenerate sequences related to a specific polypeptide sequence, i.e. all nucleic acids having a sequence that encodes one particular polypeptide sequence as well as all nucleic acids, including degenerate nucleic acids, encoding the disclosed variants and derivatives of the protein sequences. Thus, while each particular nucleic acid sequence may not be written out herein, it is understood that each and every sequence is in fact disclosed and described herein through the disclosed polypeptide sequences.
  • nucleic acid molecules capable of encoding any of the peptides described herein.
  • nucleic acid molecules capable of encoding a peptide comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • nucleic acid molecules capable of encoding a peptide comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and wherein the carrier epitope is at the N terminus of the peptide.
  • nucleic acid molecules capable of encoding a peptide comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and wherein the modified medin peptide is at the C-terminus of the peptide.
  • nucleic acid molecules capable of encoding a peptide comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and wherein the modified medin peptide or fragment thereof is 12-18 amino acids long.
  • nucleic acid molecules capable of encoding a peptide comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises or consists of the amino acid sequence of TQGARDFGHIQYVA (SEQ ID NO: 4) or TQGARNFGSVQFVA (SEQ ID NO: 3).
  • nucleic acid molecules capable of encoding a peptide comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises or consists of the amino acid sequence of TQGARDFGHIQYVA (SEQ ID NO: 4) or TQGARNFGSVQFVA (SEQ ID NO: 3) and wherein amino acids T at position 1 and F at position 7 of SEQ ID NO: 3 are in the D-form or wherein amino acids T at position 1 and F at position 7 of SEQ ID NO: 4 are in the D-form.
  • nucleic acid molecules capable of encoding a peptide comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of LGSSKEVTGIITQGARNFGSVQFVA (SEQ ID NO: 5) or LGTQRQVTGIITQGARDFGHIQYVA (SEQ ID NO: 6).
  • nucleic acid molecules capable of encoding a peptide comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of TGIITQGARNFGSVQFVA (SEQ ID NO: 7) or TGIITQGARDFGHIQYVA (SEQ ID NO: 8).
  • nucleic acid molecules capable of encoding a peptide comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of LGTQRQVTGIITQGARDFGHIQYVA (SEQ ID NO: 6).
  • nucleic acid molecules capable of encoding a peptide comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of TGIITQGARDFGHIQYVA (SEQ ID NO: 8).
  • nucleic acid molecules capable of encoding a peptide comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and wherein the carrier epitope is at the N terminus of the peptide, wherein the carrier epitope is a KLH protein.
  • vectors comprising a nucleic acid molecule capable of encoding any of the peptides disclosed herein.
  • vectors comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • vectors comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and wherein the carrier epitope is at the N terminus of the peptide.
  • vectors comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and wherein the modified medin peptide is at the C-terminus of the peptide.
  • vectors comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and wherein the modified medin peptide or fragment thereof is 12-18 amino acids long.
  • vectors comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises or consists of the amino acid sequence of TQGARDFGHIQYVA (SEQ ID NO: 4) or TQGARNFGSVQFVA (SEQ ID NO: 3).
  • vectors comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises or consists of the ammo acid sequence of TQGARDFGHIQYVA (SEQ ID NO: 4) or TQGARNFGSVQFVA (SEQ ID NO: 3) and wherein amino acids T at position 1 and F at position 7 of SEQ ID NO: 4 are in the D-form or wherein amino acids T at position 1 and F at position 7 of SEQ ID NO: 3 are in the D-form.
  • TQGARDFGHIQYVA SEQ ID NO: 4
  • TQGARNFGSVQFVA SEQ ID NO: 3
  • vectors comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of LGSSKEVTGIITQGARNFGSVQFVA (SEQ ID NO: 5) or LGTQRQVTGIITQGARDFGHIQYVA (SEQ ID NO: 6).
  • vectors comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of TGIITQGARNFGSVQFVA (SEQ ID NO: 7) or TGIITQGARDFGHIQYVA (SEQ ID NO: 8).
  • vectors comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of LGTQRQVTGIITQGARDFGHIQYVA (SEQ ID NO: 6).
  • vectors comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of TGIITQGARDFGHIQYVA (SEQ ID NO: 8).
  • vectors comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and wherein the carrier epitope is at the N terminus of the peptide, wherein the carrier epitope is a KLH protein.
  • Vectors that can be used herein can include plasmids, cosmids, and viruses (e.g., bacteriophage, animal viruses, and plant viruses), and artificial chromosomes (e.g., YACs).
  • Vectors can comprise targeting molecules.
  • a targeting molecule is one that directs the desired nucleic acid to a particular organ, tissue, cell, or other location in a subject's body.
  • a vector generally, brings about replication when it is associated with the proper control elements (e.g., a promoter, a stop codon, and a polyadenylation signal). Examples of vectors that are routinely used in the art include plasmids and viruses.
  • vector includes expression vectors and refers to a vector containing a nucleic acid sequence coding for at least part of a gene product capable of being transcribed.
  • the expression vector comprises a virus or an engineered vector derived from a viral genome.
  • expression vector is a vector that includes a regulatory region. A variety' of host/expression vector combinations can be used to express the nucleic acid sequences disclosed herein.
  • expression vectors include but are not limited to plasmids and viral vectors derived from, for example, bacteriophages, retroviruses (e.g., lentiviruses), and other viruses (e.g., adenoviruses, poxviruses, herpesviruses, baculovirus, tobacco mosaic virus and adeno- associated viruses).
  • retroviruses e.g., lentiviruses
  • viruses e.g., adenoviruses, poxviruses, herpesviruses, baculovirus, tobacco mosaic virus and adeno- associated viruses.
  • Vectors and expression systems are commercially available and known to one skilled in the art.
  • cells comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • cells comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • cells comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and wherein the carrier epitope is at the N terminus of the peptide.
  • cells comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and wherein the carrier epitope is at the N terminus of the peptide.
  • cells comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and wherein the modified medin peptide is at the C-terminus of the peptide.
  • cells comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and wherein the modified medin peptide is at the C-terminus of the peptide.
  • cells comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and wherein the modified medin peptide or fragment thereof is 12-18 amino acids long.
  • cells comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and wherein the modified medin peptide or fragment thereof is 12-18 amino acids long.
  • peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises or consists of the amino acid sequence of TQGARDFGHIQYVA (SEQ ID NO: 4) or TQGARNFGSVQFVA (SEQ ID NO: 3).
  • cells comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises or consists of the ammo acid sequence of TQGARDFGHIQYVA (SEQ ID NO: 4) or TQGARNFGSVQFVA (SEQ ID NO: 3).
  • a peptide comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises or consists of the amino acid sequence of TQGARDFGHIQYVA (SEQ ID NO: 4) or TQGARNFGSVQFVA (SEQ ID NO: 3) and wherein amino acids T at position 1 and F at position 7 of SEQ ID NO: 4 are in the D-form or wherein amino acids T at position 1 and F at position 7 of SEQ ID NO: 3 are in the D-form.
  • cells comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises or consists of the ammo acid sequence of TQGARDFGHIQYVA (SEQ ID NO: 4) or TQGARNFGSVQFVA (SEQ ID NO: 3) and wherein amino acids T at position 1 and F at position 7 of SEQ ID NO: 4 are in the D-form or wherein amino acids T at position 1 and F at position 7 of SEQ ID NO: 3 are in the D-form.
  • TQGARDFGHIQYVA SEQ ID NO: 4
  • TQGARNFGSVQFVA SEQ ID NO: 3
  • a peptide comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of LGSSKEVTGIITQGARNFGSVQFVA (SEQ ID NO: 5) or LGTQRQVTGIITQGARDFGHIQYVA (SEQ ID NO: 6).
  • cells comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of LGSSKEVTGIITQGARNFGSVQFVA (SEQ ID NO: 5) or LGTQRQVTGIITQGARDFGHIQYVA (SEQ ID NO: 6).
  • peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of TGIITQGARNFGSVQFVA (SEQ ID NO: 7) or TGIITQGARDFGHIQYVA (SEQ ID NO: 8).
  • cells comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of TGIITQGARNFGSVQFVA (SEQ ID NO: 7) or TGIITQGARDFGHIQYVA (SEQ ID NO: 8).
  • cells comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of LGTQRQVTGIITQGARDFGHIQYVA (SEQ ID NO: 6)
  • cells comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of LGTQRQVTGIITQGARDFGHIQYVA (SEQ ID NO: 6).
  • peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of TGIITQGARDFGHIQYVA (SEQ ID NO: 8).
  • cells comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of TGIITQGARDFGHIQYVA (SEQ ID NO: 8).
  • cells comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and wherein the carrier epitope is at the N terminus of the peptide, wherein the carrier epitope is a KLH protein.
  • cells comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and wherein the carrier epitope is at the N terminus of the peptide, wherein the carrier epitope is a KLH protein.
  • Examples of cells include, but are not limited to endothelial cells, smooth muscle cells, neurons, astrocytes, microglia, oligodendrocytes, immortalized cell lines such as HEK393 and cancer cell lines.
  • compositions comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • compositions comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a earner epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • compositions comprising cells, wherein the cells comprise a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • compositions comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and wherein the carrier epitope is at the N terminus of the peptide.
  • compositions comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a earner epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and wherein the carrier epitope is at the N terminus of the peptide.
  • compositions comprising cells, wherein the cells comprise a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and wherein the carrier epitope is at the N terminus of the peptide.
  • compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and wherein the carrier epitope is at the N terminus of the peptide.
  • compositions comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and wherein the modified medin peptide is at the C-terminus of the peptide.
  • compositions comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and wherein the modified medin peptide is at the C-terminus of the peptide.
  • compositions comprising cells, wherein the cells comprise a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and wherein the modified medin peptide is at the C-terminus of the peptide.
  • compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and wherein the modified medin peptide is at the C-terminus of the peptide.
  • compositions comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and wherein the modified medin peptide or fragment thereof is 12-18 amino acids long.
  • compositions comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a earner epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and wherein the modified medin peptide or fragment thereof is 12-18 amino acids long.
  • compositions comprising cells, wherein the cells comprise a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and wherein the modified medin peptide or fragment thereof is 12-18 amino acids long.
  • compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and wherein the modified medin peptide or fragment thereof is 12-18 amino acids long.
  • compositions comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises or consists of the amino acid sequence of TQGARDFGHIQYVA (SEQ ID NO: 4) or TQGARNFGSVQFVA (SEQ ID NO: 3).
  • compositions comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises or consists of the amino acid sequence of TQGARDFGHIQYVA (SEQ ID NO: 4) or TQGARNFGSVQFVA (SEQ ID NO: 3).
  • compositions comprising cells, wherein the cells comprise a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises or consists of the amino acid sequence of TQGARDFGHIQYVA (SEQ ID NO: 4) or TQGARNFGSVQFVA (SEQ ID NO: 3).
  • compositions comprising cells, wherein the cells comprise a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises or consists of the amino acid sequence of TQGARDFGHIQYVA (SEQ ID NO: 4) or TQGARNFGSVQFVA (SEQ ID NO: 3).
  • compositions comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises or consists of the amino acid sequence of TQGARDFGHIQYVA (SEQ ID NO: 4) or TQGARNFGSVQFVA (SEQ ID NO: 3) and wherein amino acids T at position 1 and F at position 7 of SEQ ID NO: 4 are in the D-form or wherein amino acids T at position 1 and F at position 7 of SEQ ID NO: 3 are in the D-form.
  • TQGARDFGHIQYVA SEQ ID NO: 4
  • TQGARNFGSVQFVA SEQ ID NO: 3
  • compositions comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a earner epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises or consists of the ammo acid sequence of TQGARDFGHIQYVA (SEQ ID NO: 4) or TQGARNFGSVQFVA (SEQ ID NO: 3) and wherein amino acids T at position 1 and F at position 7 of SEQ ID NO: 4 are in the D-form or wherein amino acids T at position 1 and F at position 7 of SEQ ID NO: 3 are in the D-form.
  • TQGARDFGHIQYVA SEQ ID NO: 4
  • TQGARNFGSVQFVA SEQ ID NO: 3
  • compositions comprising cells, wherein the cells comprise a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises or consists of the amino acid sequence of TQGARDFGHIQYVA (SEQ ID NO: 4) or TQGARNFGSVQFVA (SEQ ID NO: 3) and wherein amino acids T at position 1 and F at position 7 of SEQ ID NO: 4 are in the D-form or wherein amino acids T at position 1 and F at position 7 of SEQ ID NO: 3 are in the D-form.
  • TQGARDFGHIQYVA SEQ ID NO: 4
  • TQGARNFGSVQFVA SEQ ID NO: 3
  • compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises or consists of the amino acid sequence of TQGARDFGHIQYVA (SEQ ID NO: 4) or TQGARNFGSVQFVA (SEQ ID NO: 3) and wherein amino acids T at position 1 and F at position 7 of SEQ ID NO: 4 are in the D-form or wherein amino acids T at position 1 and F at position 7 of SEQ ID NO: 3 are in the D-form.
  • TQGARDFGHIQYVA SEQ ID NO: 4
  • TQGARNFGSVQFVA SEQ ID NO: 3
  • compositions comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of LGSSKEVTGIITQGARNFGSVQFVA (SEQ ID NO: 5) or LGTQRQVTGIITQGARDFGHIQYVA (SEQ ID NO: 6).
  • compositions comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a earner epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of LGSSKEVTGIITQGARNFGSVQFVA (SEQ ID NO: 5) or LGTQRQVTGIITQGARDFGHIQYVA (SEQ ID NO: 6).
  • compositions comprising cells, wherein the cells comprise a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of LGSSKEVTGIITQGARNFGSVQFVA (SEQ ID NO: 5) or LGTQRQVTGIITQGARDFGHIQYVA (SEQ ID NO: 6).
  • compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of LGSSKEVTGIITQGARNFGSVQFVA (SEQ ID NO: 5) or LGTQRQVTGIITQGARDFGHIQYVA (SEQ ID NO: 6).
  • compositions comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of TGIITQGARNFGSVQFVA (SEQ ID NO: 7) or TGIITQGARDFGHIQYVA (SEQ ID NO: 8).
  • compositions comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a earner epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of TGIITQGARNFGSVQFVA (SEQ ID NO: 7) or TGIITQGARDFGHIQYVA (SEQ ID NO: 8).
  • compositions comprising cells, wherein the cells comprise a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of TGIITQGARNFGSVQFVA (SEQ ID NO: 7) or TGIITQGARDFGHIQYVA (SEQ ID NO: 8).
  • compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of TGIITQGARNFGSVQFVA (SEQ ID NO: 7) or TGIITQGARDFGHIQYVA (SEQ ID NO: 8).
  • compositions comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of LGTQRQVTGIITQGARDFGHIQYVA (SEQ ID NO: 6).
  • compositions comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of LGTQRQVTGIITQGARDFGHIQYVA (SEQ ID NO: 6).
  • compositions comprising cells, wherein the cells comprise a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide or fragment thereof comprises or consists of the ammo acid sequence of LGTQRQVTGIITQGARDFGHIQYVA (SEQ ID NO: 6).
  • compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of LGTQRQVTGIITQGARDFGHIQYVA (SEQ ID NO: 6).
  • compositions comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of TGIITQGARDFGHIQYVA (SEQ ID NO: 8).
  • compositions comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of TGIITQGARDFGHIQYVA (SEQ ID NO: 8).
  • compositions comprising cells, wherein the cells comprise a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of TGIITQGARDFGHIQYVA (SEQ ID NO: 8).
  • compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide or fragment thereof comprises or consists of the amino acid sequence of TGIITQGARDFGHIQYVA (SEQ ID NO: 8).
  • compositions comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and wherein the carrier epitope is at the N terminus of the peptide, wherein the carrier epitope is a KLH protein.
  • compositions comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and wherein the carrier epitope is at the N terminus of the peptide, wherein the carrier epitope is a KLH protein.
  • compositions comprising cells, wherein the cells comprise a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and wherein the carrier epitope is at the N terminus of the peptide, wherein the carrier epitope is a KLH protein.
  • compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form and wherein the carrier epitope is at the N terminus of the peptide, wherein the carrier epitope is a KLH protein.
  • compositions comprising any of the peptides, nucleic acid molecules, vectors, cells and compositions disclosed herein and a pharmaceutically acceptable carrier.
  • a material or carrier that would be selected to minimize any degradation of the active ingredient and to minimize any adverse side effects in the subject, as would be well known to one of skill in the art.
  • carriers include dimyristoylphosphatidyl (DMPC), phosphate buffered saline or a multivesicular liposome.
  • DMPC dimyristoylphosphatidyl
  • PG:PC:Cholesterol:peptide or PC:peptide can be used as carriers in this invention.
  • Other suitable pharmaceutically acceptable carriers and their formulations are described in Remington: The Science and Practice of Pharmacy (19th ed.) ed. A.R. Gennaro, Mack Publishing Company, Easton, PA 1995.
  • an appropriate amount of pharmaceutically-acceptable salt is used in the formulation to render the formulation isotonic.
  • the pharmaceutically-acceptable carrier include, but are not limited to, saline. Ringer's solution and dextrose solution. The pH of the solution can be from about 5 to about 8, or from about 7 to about 7.5.
  • Further carriers include sustained release preparations such as semi-permeable matrices of solid hydrophobic polymers containing the composition, which matrices are in the form of shaped articles, e.g., films, stents (which are implanted in vessels during an angioplasty procedure), liposomes or microparticles.
  • compositions can also include carriers, thickeners, diluents, buffers, preservatives and the like, as long as the intended activity of the polypeptide, peptide, nucleic acid, vector of the invention is not compromised.
  • Pharmaceutical compositions may also include one or more active ingredients (in addition to the composition of the invention) such as antimicrobial agents, anti-inflammatory' agents, anesthetics, and the like. The pharmaceutical composition may be administered in a number of ways depending on whether local or systemic treatment is desired, and on the area to be treated.
  • Preparations of parenteral administration include sterile aqueous or non-aqueous solutions, suspensions, and emulsions.
  • non-aqueous solvents are propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable organic esters such as ethyl oleate.
  • Aqueous carriers include water, alcoholic/aqueous solutions, emulsions or suspensions, including saline and buffered media.
  • Parenteral vehicles include sodium chloride solution, Ringer’s dextrose, dextrose and sodium chloride, lactated Ringer’s, or fixed oils.
  • Intravenous vehicles include fluid and nutrient replenishers, electrolyte replenishers (such as those based on Ringer’s dextrose), and the like. Preservatives and other additives may also be present such as. for example, antimicrobials, anti-oxidants, chelating agents, and inert gases and the like.
  • Formulations for optical administration may include ointments, lotions, creams, gels, drops, suppositories, sprays, liquids and powders. Conventional pharmaceutical carriers, aqueous, powder or oily bases, thickeners and the like may be necessary or desirable.
  • Compositions for oral administration include powders or granules, suspensions or solutions in water or non-aqueous media, capsules, sachets, or tablets. Thickeners, flavorings, diluents, emulsifiers, dispersing aids, or binders may be desirable.
  • compositions may potentially be administered as a pharmaceutically acceptable acid- or baseaddition salt, formed by reaction with inorganic acids such as hydrochloric acid, hydrobromic acid, perchloric acid, nitric acid, thiocyanic acid, sulfuric acid, and phosphoric acid, and organic acids such as formic acid, acetic acid, propionic acid, glycolic acid, lactic acid, pyruvic acid, oxalic acid, malonic acid, succinic acid, maleic acid, and fumaric acid, or by reaction with an inorganic base such as sodium hydroxide, ammonium hydroxide, potassium hydroxide, and organic bases such as mon-, di-, trialkyl and aryl amines and substituted ethanolamines.
  • inorganic acids such as hydrochloric acid, hydrobromic acid, perchloric acid, nitric acid, thiocyanic acid, sulfuric acid, and phosphoric acid
  • organic acids such as formic acid, acetic acid, propionic acid,
  • Disclosed herein are methods of disrupting medin toxicity in a subject in need thereof comprising administering any one of the disclosed peptides, nucleic acids, vectors, cells, compositions or pharmaceutical compositions to the subject.
  • the method generates an immune response in said subject.
  • the method generates an immune response specific to the peptide.
  • the immune response to the peptide does not generate an immune response or minimal immune response to MFGE8.
  • a peptide comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • Disclosed herein are methods for disrupting medin toxicity in a subject in need thereof comprising administering an effective amount of a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • Disclosed herein are methods for disrupting medin toxicity in a subject in need thereof comprising administering an effective amount of a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • Disclosed herein are methods for disrupting medin toxicity in a subject in need thereof comprising administering an effective amount of a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • Disclosed herein are methods for disrupting medin toxicity in a subject in need thereof comprising administering an effective amount of a composition comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • Disclosed herein are methods for disrupting medin toxicity in a subject in need thereof comprising administering an effective amount of a composition comprising a nucleic acid capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • Disclosed herein are methods for disrupting medin toxicity in a subject in need thereof comprising administering an effective amount of a composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • Disclosed herein are methods for disrupting medin toxicity in a subject in need thereof comprising administering an effective amount of a composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • Disclosed herein are methods for disrupting medin toxicity in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a pharmaceutical composition comprising a nucleic acid capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • Disclosed herein are methods for disrupting medin toxicity in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises : a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises : a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • compositions comprising a composition, wherein the composition comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • Disclosed are methods of reversing medin-induced endothelial activation in a subject in need thereof comprising administering to the subject an effective amount of any one of the peptides, nucleic acids, cells, compositions or pharmaceutical compositions disclosed herein to the subject.
  • the method generates an immune response in said subject.
  • the method generates an immune response specific to the peptide.
  • the immune response to the peptide does not generate an immune response or minimal immune response to MFGE8.
  • a peptide comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • Disclosed are methods of reversing medin-induced endothelial activation in a subject in need thereof comprising administering an effective amount of a cell comprising a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises : a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • Disclosed are methods of reversing medin-induced endothelial activation in a subj ect in need thereof comprising administering an effective amount of a cell comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • Disclosed are methods of reversing medin-induced endothelial activation in a subject in need thereof comprising administering an effective amount of a composition comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • Disclosed are methods of reversing medin-induced endothelial activation in a subject in need thereof comprising administering an effective amount of a composition comprising a nucleic acid capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • Disclosed are methods of reversing medin-induced endothelial activation in a subj ect in need thereof comprising administering an effective amount of a composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • Disclosed are methods of reversing medin-induced endothelial activation in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • Disclosed are methods of reversing medin-induced endothelial activation in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a nucleic acid capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • Disclosed are methods of reversing medin-induced endothelial activation in a subj ect in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a composition, wherein the composition comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form. 3.
  • Disclosed are methods of inducing an immune response in a subject in need thereof comprising administering to the subject an effective amount of any one of the disclosed peptides, nucleic acids, vectors, cells, compositions or pharmaceutical compositions.
  • the method generates an immune response in said subject.
  • the method generates an immune response specific to the peptide.
  • the immune response to the peptide does not generate an immune response or minimal immune response to MFGE8.
  • a peptide comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a nucleic acid molecule capable of encoding a peptide comprisies: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a cell comprising a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a cell comprising a peptide
  • the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a composition comprising a peptide wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a composition comprising a nucleic acid capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a pharmaceutical composition comprising a peptide wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a pharmaceutical composition comprising a nucleic acid capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a pharmaceutical composition comprising a composition, wherein the composition comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • Disclosed are methods of vaccinating a subject in need thereof comprising administering to the subject an effective amount any one of the disclosed peptides, nucleic acids, vectors, cells, compositions or pharmaceutical compositions.
  • the method generates an immune response in said subject.
  • the method generates an immune response specific to the peptide.
  • the immune response to the peptide does not generate an immune response or minimal immune response to MFGE8.
  • a method of vaccinating a subject in need thereof comprising administering an effective amount of a peptide comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • the method generates an immune response in said subject.
  • the method generates an immune response specific to the peptide.
  • the immune response to the peptide does not generate an immune response or minimal immune response to MFGE8.
  • a method of vaccinating a subject in need thereof comprising administering an effective amount of a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • the method generates an immune response in said subject.
  • the method generates an immune response specific to the peptide.
  • the immune response to the peptide does not generate an immune response or minimal immune response to MFGE8.
  • a method of vaccinating a subject in need thereof comprising administering an effective amount of a cell comprising a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • the method generates an immune response in said subject.
  • the method generates an immune response specific to the peptide.
  • the immune response to the peptide does not generate an immune response or minimal immune response to MFGE8.
  • a method of vaccinating a subject in need thereof comprising administering an effective amount of a cell comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • the method generates an immune response in said subject.
  • the method generates an immune response specific to the peptide.
  • the immune response to the peptide does not generate an immune response or minimal immune response to MFGE8.
  • a method of vaccinating a subject in need thereof comprising administering an effective amount of a composition comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • the method generates an immune response in said subject.
  • the method generates an immune response specific to the peptide.
  • the immune response to the peptide does not generate an immune response or minimal immune response to MFGE8.
  • a method of vaccinating a subject in need thereof comprising administering an effective amount of a composition comprising a nucleic acid capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • the method generates an immune response in said subject.
  • the method generates an immune response specific to the peptide.
  • the immune response to the peptide does not generate an immune response or minimal immune response to MFGE8.
  • a method of vaccinating a subject in need thereof comprising administering an effective amount of a composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • the method generates an immune response in said subject.
  • the method generates an immune response specific to the peptide.
  • the immune response to the peptide does not generate an immune response or minimal immune response to MFGE8.
  • a method of vaccinating a subject in need thereof comprising administering an effective amount of a composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • the method generates an immune response in said subject.
  • the method generates an immune response specific to the peptide.
  • the immune response to the peptide does not generate an immune response or minimal immune response to MFGE8.
  • a method of vaccinating a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • the method generates an immune response in said subject.
  • the method generates an immune response specific to the peptide.
  • the immune response to the peptide does not generate an immune response or minimal immune response to MFGE8.
  • a method of vaccinating a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a nucleic acid capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • the method generates an immune response in said subject.
  • the method generates an immune response specific to the peptide.
  • the immune response to the peptide does not generate an immune response or minimal immune response to MFGE
  • a method of vaccinating a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • the method generates an immune response in said subject.
  • the method generates an immune response specific to the peptide.
  • the immune response to the peptide does not generate an immune response or minimal immune response to MFGE8.
  • a method of vaccinating a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • the method generates an immune response in said subject.
  • the method generates an immune response specific to the peptide. In some aspects, the immune response to the peptide does not generate an immune response or minimal immune response to MFGE8.
  • a method of vaccinating a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a composition, wherein the composition comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • the method generates an immune response in said subject. In some aspects, the method generates an immune response specific to the peptide. In some aspects, the immune response to the
  • Disclosed are methods of attenuating medin-induced vascular dysfunction in a subject in need thereof comprising administering to the subject an effective amount any one of the disclosed peptides, nucleic acids, vectors, cells, compositions or pharmaceutical compositions.
  • the method generates an immune response in said subject.
  • the method generates an immune response specific to the peptide.
  • the immune response to the peptide does not generate an immune response or minimal immune response to MFGE8.
  • a method of attenuating medin-induced vascular dysfunction in a subject in need thereof comprising administering an effective amount of a peptide comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of attenuating medin-induced vascular dysfunction in a subject in need thereof comprising administering an effective amount of a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of attenuating medin-induced vascular dysfunction in a subject in need thereof comprising administering an effective amount of a cell comprising a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of attenuating medin-induced vascular dysfunction in a subject in need thereof comprising administering an effective amount of a cell comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of atenuating medin-induced vascular dysfunction in a subject in need thereof comprising administering an effective amount of a composition comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of atenuating medin-induced vascular dysfunction in a subject in need thereof comprising administering an effective amount of a composition comprising a nucleic acid capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of atenuating medin-induced vascular dysfunction in a subject in need thereof comprising administering an effective amount of a composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a earner epitope, b) a cysteine residue, and c) a modified medin peptide.
  • the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of attenuating medin-induced vascular dysfunction in a subject in need thereof comprising administering an effective amount of a composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of attenuating medin-induced vascular dysfunction in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of attenuating medin-induced vascular dysfunction in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a nucleic acid capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of attenuating medin-induced vascular dysfunction in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of attenuating medin-induced vascular dysfunction in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of attenuating medin-induced vascular dysfunction in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a composition, wherein the composition comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • Disclosed are methods of modulating vascular disease in a subject in need thereof comprising administering to the subject an effective amount any one of the disclosed peptides, nucleic acids, vectors, cells, compositions or pharmaceutical compositions.
  • the method generates an immune response in said subject.
  • the method generates an immune response specific to the peptide.
  • the immune response to the peptide does not generate an immune response or minimal immune response to MFGE8.
  • a method of modulating vascular disease in a subj ect in need thereof comprising administering an effective amount of a peptide comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating vascular disease in a subject in need thereof comprising administering an effective amount of a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating vascular disease in a subject in need thereof comprising administering an effective amount of a cell comprising a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating vascular disease in a subject in need thereof comprising administering an effective amount of a cell comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating vascular disease in a subj ect in need thereof comprising administering an effective amount of a composition comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating vascular disease in a subject in need thereof comprising administering an effective amount of a composition comprising a nucleic acid capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating vascular disease in a subject in need thereof comprising administering an effective amount of a composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating vascular disease in a subject in need thereof comprising administering an effective amount of a composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating vascular disease in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating vascular disease in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a nucleic acid capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating vascular disease in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating vascular disease in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating vascular disease in a subj ect in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a composition, wherein the composition comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • Disclosed are methods of modulating medin aggregation in a subject in need thereof comprising administering to the subject an effective amount any one of the disclosed peptides, nucleic acids, vectors, cells, compositions or pharmaceutical compositions.
  • the method generates an immune response in said subject.
  • the method generates an immune response specific to the peptide.
  • the immune response to the peptide does not generate an immune response or minimal immune response to MFGE8.
  • a method of modulating medin aggregation in a subject in need thereof comprising administering an effective amount of a peptide comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating medin aggregation in a subject in need thereof comprising administering an effective amount of a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating medin aggregation in a subject in need thereof comprising administering an effective amount of a cell comprising a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating medin aggregation in a subject in need thereof comprising administering an effective amount of a cell comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating medin aggregation in a subject in need thereof comprising administering an effective amount of a composition comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating medin aggregation in a subj ect in need thereof comprising administering an effective amount of a composition comprising a nucleic acid capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating medin aggregation in a subject in need thereof comprising administering an effective amount of a composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating medin aggregation in a subject in need thereof comprising administering an effective amount of a composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating medin aggregation in a subj ect in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating medin aggregation in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a nucleic acid capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating medin aggregation in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating medin aggregation in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating medin aggregation in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a composition, wherein the composition comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • Methods for Treating or Preventing Vascular Dysfunction or Inflammation comprising administering to the subject an effective amount any one of the disclosed peptides, nucleic acids, vectors, cells, compositions or pharmaceutical compositions.
  • the method generates an immune response in said subject.
  • the method generates an immune response specific to the peptide.
  • the immune response to the peptide does not generate an immune response or minimal immune response to MFGE8.
  • a method of preventing vascular dysfunction in a subj ect in need thereof comprising administering an effective amount of a peptide comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of preventing vascular dysfunction in a subject in need thereof comprising administering an effective amount of a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of preventing vascular dysfunction in a subject in need thereof comprising administering an effective amount of a cell comprising a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of preventing vascular dysfunction in a subj ect in need thereof comprising administering an effective amount of a cell comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of preventing vascular dysfunction in a subject in need thereof comprising administering an effective amount of a composition comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of preventing vascular dy sfunction in a subject in need thereof comprising administering an effective amount of a composition comprising a nucleic acid capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of preventing vascular dysfunction in a subj ect in need thereof comprising administering an effective amount of a composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of preventing vascular dysfunction in a subject in need thereof comprising administering an effective amount of a composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of preventing vascular dysfunction in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of preventing vascular dysfunction in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a nucleic acid capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of preventing vascular dysfunction in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of preventing vascular dysfunction in a subj ect in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a earner epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of preventing vascular dysfunction in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a composition, wherein the composition comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • Disclosed are methods of preventing vascular inflammation in a subject in need thereof comprising administering to the subject an effective amount any one of the disclosed peptides, nucleic acids, cells, compositions or pharmaceutical compositions.
  • a method of preventing vascular inflammation in a subject in need thereof comprising administering an effective amount of a peptide comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of preventing vascular inflammation in a subject in need thereof comprising administering an effective amount of a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of preventing vascular inflammation in a subject in need thereof comprising administering an effective amount of a cell comprising a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of preventing vascular inflammation in a subject in need thereof comprising administering an effective amount of a cell comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of preventing vascular inflammation in a subj ect in need thereof comprising administering an effective amount of a composition comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of preventing vascular inflammation in a subject in need thereof comprising administering an effective amount of a composition comprising a nucleic acid capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of preventing vascular inflammation in a subject in need thereof comprising administering an effective amount of a composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of preventing vascular inflammation in a subject in need thereof comprising administering an effective amount of a composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of preventing vascular inflammation in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of preventing vascular inflammation in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a nucleic acid capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of preventing vascular inflammation in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of preventing vascular inflammation in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of preventing vascular inflammation in a subj ect in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a composition, wherein the composition comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • IL-8 interleukin
  • IL-6 intercellular adhesion molecule- 1
  • PAI-1 plasminogen activator inhibitor-1
  • IL-8 interleukin
  • ICM-1 intercellular adhesion molecule-1
  • PAI-1 plasminogen activator inhibitor-1
  • the method generates an immune response in said subject.
  • the method generates an immune response specific to the peptide.
  • the immune response to the peptide does not generate an immune response or minimal immune response to MFGE8.
  • a method of reducing interleukin (IL)-8, IL-6, intercellular adhesion molecule-1 (ICAM-1) or plasminogen activator inhibitor-1 (PAI-1) levels in a subject in need thereof comprising administenng an effective amount of a peptide comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of reducing interleukin (IL)-8, IL-6, intercellular adhesion molecule-1 (ICAM-1) or plasminogen activator inhibitor-1 (PAI-1) levels in a subject in need thereof comprising administering an effective amount of a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • IL interleukin
  • IAM-1 intercellular adhesion molecule-1
  • PAI-1 plasminogen activator inhibitor-1
  • a method of reducing interleukin (IL)-8, IL-6, intercellular adhesion molecule-1 (ICAM-1) or plasminogen activator inhibitor-1 (PAI-1) levels in a subject in need thereof comprising administering an effective amount of a cell comprising a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • IL interleukin
  • IAM-1 intercellular adhesion molecule-1
  • PAI-1 plasminogen activator inhibitor-1
  • a method of reducing interleukin (IL)-8, IL-6, intercellular adhesion molecule-1 (ICAM-1) or plasminogen activator inhibitor-1 (PAI-1) levels in a subject in need thereof comprising administering an effective amount of a cell comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • IL interleukin
  • IAM-1 intercellular adhesion molecule-1
  • PAI-1 plasminogen activator inhibitor-1
  • a method of reducing interleukin (IL)-8, IL-6, intercellular adhesion molecule-1 (ICAM-1) or plasminogen activator inhibitor-1 (PAI-1) levels in a subject in need thereof comprising administering an effective amount of a composition comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • IL interleukin
  • IAM-1 intercellular adhesion molecule-1
  • PAI-1 plasminogen activator inhibitor-1
  • a method of reducing interleukin (IL)-8, IL-6, intercellular adhesion molecule-1 (ICAM-1) or plasminogen activator inhibitor-1 (PAI-1) levels in a subject in need thereof comprising administering an effective amount of a composition comprising a nucleic acid capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • IL interleukin
  • IAM-1 intercellular adhesion molecule-1
  • PAI-1 plasminogen activator inhibitor-1
  • a method of reducing interleukin (IL)-8, IL-6, intercellular adhesion molecule-1 (ICAM-1) or plasminogen activator inhibitor-1 (PAI-1) levels in a subject in need thereof comprising administering an effective amount of a composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • IL interleukin
  • IAM-1 intercellular adhesion molecule-1
  • PAI-1 plasminogen activator inhibitor-1
  • a method of reducing interleukin (IL)-8, IL-6, intercellular adhesion molecule-1 (ICAM-1) or plasminogen activator inhibitor-1 (PAI-1) levels in a subject in need thereof comprising administenng an effective amount of a composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • IL interleukin
  • IAM-1 intercellular adhesion molecule-1
  • PAI-1 plasminogen activator inhibitor-1
  • a method of reducing interleukin (IL)-8, IL-6, intercellular adhesion molecule-1 (ICAM-1) or plasminogen activator inhibitor-1 (PAI-1) levels in a subject in need thereof comprising administenng an effective amount of a pharmaceutical composition comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of reducing interleukin (IL)-8, IL-6, intercellular adhesion molecule-1 (ICAM-1) or plasminogen activator inhibitor-1 (PAI-1) levels in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a nucleic acid capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • IL interleukin
  • IAM-1 intercellular adhesion molecule-1
  • PAI-1 plasminogen activator inhibitor-1
  • a method of reducing interleukin (IL)-8, IL-6, intercellular adhesion molecule-1 (ICAM-1) or plasminogen activator inhibitor-1 (PAI-1) levels in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • IL interleukin
  • IAM-1 intercellular adhesion molecule-1
  • PAI-1 plasminogen activator inhibitor-1
  • a method of reducing interleukin (IL)-8, IL-6, intercellular adhesion molecule-1 (ICAM-1) or plasminogen activator inhibitor-! (PAI-1) levels in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • IL interleukin
  • IAM-1 intercellular adhesion molecule-1
  • PAI-1 plasminogen activator inhibitor-!
  • a method of reducing interleukin (IL)-8, IL-6, intercellular adhesion molecule-1 (ICAM-1) or plasminogen activator inhibitor-1 (PALI) levels in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a composition, wherein the composition comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • IL interleukin
  • IAM-1 intercellular adhesion molecule-1
  • PALI plasminogen activator inhibitor-1
  • the reducing is compared in the same subject before and after administration of the peptides disclosed herein. In some aspects, the reducing is compared to a similarly situated subject.
  • Disclosed are methods of modulating or preventing cerebrovascular dysfunction in a subject in need thereof comprising administering to the subject an effective amount any one of the disclosed peptides, nucleic acids, vectors, cells, compositions or pharmaceutical compositions.
  • the method generates an immune response in said subject.
  • the method generates an immune response specific to the peptide.
  • the immune response to the peptide does not generate an immune response or minimal immune response to MFGE8.
  • a method of modulating or preventing cerebrovascular dysfunction in a subject in need thereof comprising administering an effective amount of a peptide comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing cerebrovascular dysfunction in a subject in need thereof comprising administering an effective amount of a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing cerebrovascular dysfunction in a subject in need thereof comprising administering an effective amount of a cell comprising a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing cerebrovascular dysfunction in a subject in need thereof comprising administering an effective amount of a cell comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing cerebrovascular dysfunction in a subject in need thereof comprising administering an effective amount of a composition comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing cerebrovascular dysfunction in a subject in need thereof comprising administering an effective amount of a composition comprising a nucleic acid capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing cerebrovascular dysfunction in a subject in need thereof comprising administering an effective amount of a composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing cerebrovascular dysfunction in a subject in need thereof comprising administering an effective amount of a composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing cerebrovascular dysfunction in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing cerebrovascular dysfunction in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a nucleic acid capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing cerebrovascular dysfunction in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a cell, wherin the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing cerebrovascular dysfunction in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing cerebrovascular dysfunction in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a composition, wherein the composition comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • Disclosed are methods of modulating or preventing cognitive dysfunction in a subject in need thereof comprising administering to the subject an effective amount any one of the disclosed peptides, nucleic acids, cells, compositions or pharmaceutical compositions.
  • a method of modulating or preventing cognitive dysfunction in a subject in need thereof comprising administering an effective amount of a peptide comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an ammo acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing cognitive dysfunction in a subject in need thereof comprising administering an effective amount of a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing cognitive dysfunction in a subject in need thereof comprising administering an effective amount of a cell comprising a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing cognitive dysfunction in a subject in need thereof comprising administering an effective amount of a cell comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing cognitive dysfunction in a subject in need thereof comprising administering an effective amount of a composition comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing cognitive dysfunction in a subject in need thereof comprising administering an effective amount of a composition comprising a nucleic acid capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing cognitive dysfunction in a subject in need thereof comprising administering an effective amount of a composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing cognitive dysfunction in a subject in need thereof comprising administering an effective amount of a composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing cognitive dysfunction in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing cognitive dysfunction in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a nucleic acid capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing cognitive dysfunction in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an ammo acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing cognitive dysfunction in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing cognitive dysfunction in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a composition, wherein the composition comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • Disclosed are methods of modulating or preventing neurodegeneration in a subject in need thereof comprising administering to the subject an effective amount any one of the disclosed peptides, nucleic acids, cells, compositions or pharmaceutical compositions.
  • a method of modulating or preventing neurodegeneration in a subj ect in need thereof comprising administering an effective amount of a peptide comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing neurodegeneration in a subj ect in need thereof comprising administering an effective amount of a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing neurodegeneration in a subj ect in need thereof comprising administering an effective amount of a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing neurodegeneration in a subject in need thereof comprising administering an effective amount of a cell comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing neurodegeneration in a subj ect in need thereof comprising administering an effective amount of a composition comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing neurodegeneration in a subj ect in need thereof comprising administering an effective amount of a composition comprising a nucleic acid capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing neurodegeneration in a subject in need thereof comprising administering an effective amount of a composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing neurodegeneration in a subj ect in need thereof comprising administering an effective amount of a composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing neurodegeneration in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing neurodegeneration in a subj ect in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a nucleic acid capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing neurodegeneration in a subj ect in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing neurodegeneration in a subj ect in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing neurodegeneration in a subj ect in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a composition, wherein the composition comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing neurovascular pathology in a subject in need thereof comprising administering an effective amount of a peptide comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing neurovascular pathology in a subject in need thereof comprising administering an effective amount of a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing neurovascular pathology' in a subject in need thereof comprising administering an effective amount of a cell comprising a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing neurovascular pathology in a subject in need thereof comprising administering an effective amount of a cell comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing neurovascular pathology in a subject in need thereof comprising administering an effective amount of a composition comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing neurovascular pathology' in a subject in need thereof comprising administering an effective amount of a composition comprising a nucleic acid capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing neurovascular pathology in a subject in need thereof comprising administering an effective amount of a composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing neurovascular pathology in a subject in need thereof comprising administering an effective amount of a composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing neurovascular pathology in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing neurovascular pathology in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a nucleic acid capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing neurovascular pathology in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing neurovascular pathology in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing neurovascular pathology in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a composition, wherein the composition comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • Disclosed are methods of modulating or preventing amyloid plaque formation in a subject in need thereof comprising administering to the subject an effective amount any one of the disclosed peptides, nucleic acids, vectors, cells, compositions or pharmaceutical compositions.
  • the method generates an immune response in said subject.
  • the method generates an immune response specific to the peptide.
  • the immune response to the peptide does not generate an immune response or minimal immune response to MFGE8.
  • a method of modulating or preventing amyloid plaque formation in a subject in need thereof comprising administering an effective amount of a peptide comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing amyloid plaque formation in a subject in need thereof comprising administering an effective amount of a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing amyloid plaque formation in a subject in need thereof comprising administering an effective amount of a cell comprising a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing amyloid plaque formation in a subject in need thereof comprising administering an effective amount of a cell comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing amyloid plaque formation in a subject in need thereof comprising administering an effective amount of a composition comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing amyloid plaque formation in a subject in need thereof comprising administering an effective amount of a composition comprising a nucleic acid capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing amyloid plaque formation in a subject in need thereof comprising administering an effective amount of a composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a earner epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing amyloid plaque formation in a subject in need thereof comprising administering an effective amount of a composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing amyloid plaque formation in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing amyloid plaque formation in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a nucleic acid capable of encoding a peptide.
  • the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing amyloid plaque formation in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing amyloid plaque formation in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of modulating or preventing amyloid plaque formation in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a composition, wherein the composition comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • Disclosed are methods of reducing the rate of growth of amyloid plaque in a subject in need thereof comprising administering to the subject an effective amount any one of the disclosed peptides, nucleic acids, cells, compositions or pharmaceutical compositions.
  • a method of reducing the rate of growth of amyloid plaque in a subject in need thereof comprising administering an effective amount of a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of reducing the rate of growth of amyloid plaque in a subject in need thereof comprising administering an effective amount of a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of reducing the rate of growth of amyloid plaque in a subject in need thereof comprising administering an effective amount of a cell comprising a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of reducing the rate of growth of amyloid plaque in a subject in need thereof comprising administering an effective amount of a cell comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of reducing the rate of growth of amyloid plaque in a subject in need thereof comprising administering an effective amount of a composition comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of reducing the rate of growth of amyloid plaque in a subject in need thereof comprising administering an effective amount of a composition comprising a nucleic acid capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of reducing the rate of growth of amyloid plaque in a subject in need thereof comprising administering an effective amount of a composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a earner epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of reducing the rate of growth of amyloid plaque in a subject in need thereof comprising administering an effective amount of a composition comprising a cell, wherein the ell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of reducing the rate of growth of amyloid plaque in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of reducing the rate of growth of amyloid plaque in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a nucleic acid capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of reducing the rate of growth of amyloid plaque in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of reducing the rate of grow th of amyloid plaque in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a method of reducing the rate of growth of amyloid plaque in a subject in need thereof comprising administering an effective amount of a pharmaceutical composition comprising a composition, wherein the composition comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • Methods of Treating Coronary Heart Disease and/or Ischemic Heart Disease comprising administering any one of the disclosed peptides, nucleic acids, vectors, cells, compositions or pharmaceutical compositions to the subject.
  • the method generates an immune response in said subject.
  • the method generates an immune response specific to the peptide.
  • the immune response to the peptide does not generate an immune response or minimal immune response to MFGE8.
  • a peptide comprising: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a pharmaceutical composition comprising a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a pharmaceutical composition comprising a nucleic acid capable of encoding a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises : a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, wherein the peptide comprises : a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form.
  • compositions comprising a composition, wherein the composition comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form and no more than 8 consecutive amino acids are in the L-form. 13.
  • a pharmaceutical composition comprising a composition, wherein the composition comprises a peptide, wherein the peptide comprises: a) a carrier epitope, b) a cysteine residue, and c) a modified medin peptide, wherein the modified medin peptide comprises an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment thereof, wherein the modified medin peptide or fragment thereof comprises at least one amino acid in the D-form
  • dosing regimens comprising at least one treatment cycle of an effective amount of any of the disclosed peptides, nucleic acid molecules, vectors, cells, compositions or pharmaceutical compositions.
  • the amino acid sequence of the peptide can be, but is not limited to, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11.
  • the modified medin peptide can be, but is not limited to, SEQ ID NO: 41, SEQ ID NO: 43, SEQ ID NO: 45, SEQ ID NO: 47, SEQ ID NO: 49, SEQ ID NO: 51, SEQ ID NO: 53, SEQ ID NO: 55, SEQ ID NO: 57, SEQ ID NO: 59, SEQ ID NO: 61, SEQ ID NO: 63, SEQ ID NO: 65, SEQ ID NO: 67, SEQ ID NO: 69, SEQ ID NO: 71, SEQ ID NO: 73, SEQ ID NO: 75 and/or SEQ ID NO: 77.
  • Treatment cycles can include the administration of different dosages of peptide, nucleic acid molecules, vectors, cells, compositions or pharmaceutical compsitions as well as administration at different time points.
  • the peptides, nucleic acid molecules, vectors, cells, compositions or pharmaceutical compsitions can be administered for varying amounts of time for up to 6 months.
  • the peptide, nucleic acid molecules, vectors, cells, compositions or pharmaceutical compositions can be administered for varying amounts of time indefinitely. In some instances, the administration can occur for up to one, two. three, four, five or six months.
  • the peptide, nucleic acid molecule, vector, cell, composition or pharmaceutical composition can be administered once a week for 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, or 24 weeks.
  • the disclosed peptides, nucleic acid molecules, vectors, cells, compositions or pharmaceutical compositions can be administered about every 3, about every 6 or about every 12 months.
  • the length of time for each treatment cycle can vary depending on the amount of peptide, nucleic acid molecule, vector, cell, composition or pharmaceutical composition administered per dosage.
  • a treatment cycle can include the administration of peptide, nucleic acid molecule, vector, cell, composition or pharmaceutical composition once, twice or three times a week.
  • the peptide, nucleic acid molecule, vector, cell, composition or pharmaceutical composition can be administered daily.
  • the peptide, nucleic acid molecule, vector, cell, composition or pharmaceutical composition can be administered once every two weeks or even once a month.
  • the peptide, nucleic acid molecule, vector, cell, composition or pharmaceutical composition can be administered every two weeks for 4, 6, 8, 10, 12, 14, 16, 18, 20, 22.
  • the treatment cycle can include administering a peptide, nucleic acid molecule, vector, cell, composition or pharmaceutical composition once a week for four weeks or once every’ two weeks for up to six months.
  • each treatment cycle includes an established length of time for administration as well as an established dosing schedule during that time frame.
  • more than one peptide, nucleic acid molecule, vector, cell, composition or pharmaceutical composition can be administered during the treatment cycles.
  • the more than one peptide, nucleic acid molecule, vector, cell, composition or pharmaceutical composition can be formulated together or in separate compositions.
  • one or more peptide, nucleic acid molecule, vector, cell, composition or pharmaceutical composition is administered in combination with one or more other therapeutic agents, including, but not limited to antibodies, nanobodies, aptamers, liposomes, antioxidants, anti-inflammatory agents, senolytic agents.
  • the dose or dosage of peptide, nucleic acid molecule, vector, cell, composition or pharmaceutical composition can vary depending on many’ factors, such as but not limited to, age, condition, sex and extent of the disease in the patient, route of administration, length of treatment cycle, or whether other drugs are included in the regimen, and can be determined by one of skill in the art.
  • Effective dosages can be determined empirically, and making such determinations is within the skill in the art.
  • the dosage ranges for the administration of the compositions are those large enough to produce the desired effect in which the disease is treated.
  • the dosage can be an amount effective to provide therapeutic effects and provide or allow for sustained therapeutic effects even after the treatment (i.e. peptide) is withdrawn.
  • the therapeutic effects can be, but are not limited to, a disruption or decrease in medin toxicity, a reversal of medin-induced endothelial activation, an induction of an immune response, a modulation, reduction or prevention of vascular disease, a modulation, reduction or prevention of medin aggregation, treating, reducing or preventing vascular dysfunction or inflammation, reducing interleukin (IL)-8, IL-6, intercellular adhesion molecule-1 (ICAM-1) and/or plasminogen activator inhibitor- 1 (PAI-1), modulating, reducing or preventing amyloid plaque formation, reducing the rate of growth of amyloid plaques.
  • IL interleukin
  • IAM-1 intercellular adhesion molecule-1
  • PAI-1 plasminogen activator inhibitor- 1
  • the therapeutic effects can be measured by markers of such as, but not limited to, interleukin (IL)-8, IL-6, intercellular adhesion molecule-1 (ICAM-1) and/or plasminogen activator inhibitor-1 (PAI- 1).
  • Other biomarkers used to measure therapeutic effects can be markers of vascular function, markers of cognitive function, markers of inflammation, such as cytokines, chemokines and/or adhesion molecules), markers of oxidative stress, and/or markers of cell death/apoptosis.
  • the therapeutic effects can be measured by imaging techniques, including MRI, intravascular ultrasound, ultrafast imaging CT scans, B-mode ultrasonography, virtual histology intravascular ultrasound, optical coherence tomography, or other known methods.
  • the dosage should not be so large as to cause adverse side effects, such as unwanted cross-reactions, anaphylactic reactions, and the like.
  • the dosage can be adjusted by the individual physician in the event of any counter-indications. Dosage can vary 7 , and can be administered in one or more dose administrations daily, for one or several days. Guidance can be found in the literature for appropriate dosages for given classes of pharmaceutical products.
  • Suitable dosages include, but are not limited to amounts between 0.01 mg/kg and 20 mg/kg.
  • disclosed herein are methods involving administering one or more of the disclosed peptide, nucleic acid molecule, vector, cell, composition or pharmaceutical composition to a subject, wherein the peptide is administered in an amount of about 0.01 mg/kg to about 20 mg/kg.
  • the concentration of the peptide can be 0.01, 0. 1, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mg/kg.
  • the peptide, nucleic acid molecule, vector, cell, composition or pharmaceutical composition dose can be administered as a bolus injection or as an infusion over one or more hours.
  • administration or delivery' of the peptides, nucleic acid molecules, vectors, cells, compositions or pharmaceutical compositions can be via a variety of mechanisms.
  • disclosed herein are methods of treating, dosing regimens and methods of using those dosing regimens to treat.
  • the dosing regimens and methods include compositions containing any one or more of the polypeptides or nucleic acids described herein that can also include a carrier such as a pharmaceutically acceptable carrier.
  • a carrier such as a pharmaceutically acceptable carrier.
  • pharmaceutical compositions comprising the peptides. nucleic acid molecules, vectors, cells and compositions disclosed herein, and a pharmaceutically acceptable carrier.
  • the disclosed peptides, nucleic acid molecules, vectors, cells, compositions or pharmaceutical compositions can be in solution or in suspension (for example, incorporated into microparticles, liposomes, or cells). These compositions can be targeted to a particular cell type via antibodies, receptors, or receptor ligands.
  • a targeting agent can be a vehicle such as an antibody conjugated liposomes; receptor mediated targeting of DNA through cell specific ligands, and highly specific retroviral targeting of cells in vivo. Any such vehicles can be part of the compositions herein.
  • targeting agents that direct the peptide, nucleic acid molecule, vector, composition or pharmaceutical composition to a medin peptide, medin polypeptide, or a medin amyloid can be included in the compositions.
  • Suitable routes of administration can be used for the disclosed compositions.
  • Suitable routes of administration can, for example, include topical, enteral, local, systemic, or parenteral.
  • administration can be epicutaneous, inhalational, enema, conjunctival, eye drops, ear drops, alveolar, nasal, intranasal, enteral, oral, intraoral, transoral, intestinal, rectal, intrarectal, transrectal, inj ection, infusion, intravenous, intraarterial, intramuscular, intracerebral, intraventricular, intracerebroventricular, intracardiac, subcutaneous, intraosseous, intradermal, intrathecal, intraperitoneal, intravesical, intracavemosal, intramedullar, intraocular, intracranial, transdermal, transmucosal, transnasal, inhalational, intracistemal, epidural, peridural, intravitreal, etc.
  • the disclosed compositions can be used in and with any
  • peptide delivery can be enhanced by the use of protective excipients. This is typically accomplished either by complexing the polypeptide with a composition to render it resistant to acidic and enzymatic hydrolysis or by packaging the polypeptide in an appropriately resistant carrier such as a liposome.
  • protective excipients typically accomplished either by complexing the polypeptide with a composition to render it resistant to acidic and enzymatic hydrolysis or by packaging the polypeptide in an appropriately resistant carrier such as a liposome.
  • Means of protecting polypeptides for oral delivery' are well known in the art (see, e.g., U.S. Pat. No. 5,391,377 describing lipid compositions for oral delivery of therapeutic agents).
  • Elevated serum half-life can be maintained by the use of sustained-release protein "packaging" systems.
  • sustained release systems are well known to those of skill in the art.
  • the ProLease biodegradable microsphere delivery' system for proteins and peptides (Tracy (1998) Biotechnol. Prog., 14: 108; Johnson et al. (1996) Nature Med. 2: 795; Herbert et al. (1998). Pharmaceut. Res. 15. 357) a dry powder composed of biodegradable polymeric microspheres containing the active agent in a polymer matrix that can be compounded as a dry formulation with or without other agents.
  • the ProLease microsphere fabrication process was specifically designed to achieve a high encapsulation efficiency while maintaining integrity of the active agent.
  • the process consists of (i) preparation of freeze-dried drug particles from bulk by spray freeze-drying the drug solution with stabilizing excipients, (ii) preparation of a drug-polymer suspension followed by sonication or homogenization to reduce the drug particle size, (iii) production of frozen drug-polymer microspheres by atomization into liquid nitrogen, (iv) extraction of the polymer solvent with ethanol, and (v) filtration and vacuum drying to produce the final dry- powder product.
  • the resulting powder contains the solid form of the active agents, which is homogeneously and rigidly dispersed within porous polymer particles.
  • the polymer most commonly used in the process poly(lactide-co-glycolide) (PLG), is both biocompatible and biodegradable.
  • Encapsulation can be achieved at low temperatures (e.g., -40° C.). During encapsulation, the protein is maintained in the solid state in the absence of water, thus minimizing water-induced conformational mobility of the protein, preventing protein degradation reactions that include water as a reactant, and avoiding organic-aqueous interfaces where proteins may undergo denaturation.
  • a preferred process uses solvents in which most proteins are insoluble, thus yielding high encapsulation efficiencies (e.g., greater than 95%).
  • one or more components of the solution can be provided as a "concentrate”, e.g., in a storage container (e.g., in a premeasured volume) ready for dilution, or in a soluble capsule ready for addition to a volume of water.
  • the peptides, nucleic acid molecules, vectors, cells, compositions or pharmaceutical compositions can be administered alone or in combination with one or more additional therapeutic agents.
  • the additional therapeutic agents are selected based on the disease or symptom to be treated.
  • a description of the various classes of suitable pharmacological agents and drugs may be found in Goodman and Gilman, The Pharmacological Basis of Therapeutics, (11th Ed.. McGraw-Hill Publishing Co.) (2005).
  • pharmaceutical compositions containing peptides can be administered in combination with one or more known therapeutic agents for treating atherosclerosis.
  • the peptides can be administered in conjunction with or followed by any of the disclosed additional therapeutics.
  • the combination therapies can include administering the peptide, nucleic acid molecule, vector, cell, composition or pharmaceutical composition and an additional therapeutic agent during the treatment cycle of a dosing regimen.
  • Medin a 50 amino acid protein formed from cleavage of parent protein milk fat globule-EGF factor 8 (MFGE8), is the protein component of the most common human amyloidosis (5, 15). Medin accumulates in the vasculature with aging (5, 15, 20), with aortic medin present in 86% of people over 55 years versus 20% in younger patients (p ⁇ 0.05)20. As shown herein, medin is present in cerebral arteries of elderly brain donors (7. 8) (FIG. 2) andcerebral arteriole medin (using scoring system from 0 to 3) is higher in AD and VaD versus non-demented donors (ND) (7).
  • MFGE8 parent protein milk fat globule-EGF factor 8
  • medin is also highly and independently associated with AD and VaD, and arterial medin content correlated with the burden of classic AD pathologic lesions, (3-amyloid (A(3) plaques and neurofibrillary tangle (NFTs) and VaD lesions (white matter changes) (7).
  • mediator is also present in coronary arteries, as shown in post-mortem histology of elderly brain and body donors (FIG. 9A-9D).
  • FIG. 9A shows a coronary artery from donor who had myocardial infarction (MI) and diabetes and tissue did not receive anti-medin primary antibody, thus serving as tissue staining control.
  • MI myocardial infarction
  • 9B-C show coronary arteries from donors who had MI and diabetes and stained with anti-medin primary' antibody (DAB staining); dark blue/brown stain (appears black on black and white print, sample regions shown with black arrows) denotes medin which is found in tunica intima (endothelial layer), tunica media (smooth muscle layer) as well as tunica adventitia of the coronary 7 arteries.
  • DAB staining dark blue/brown stain
  • tunica media smooth muscle layer
  • tunica adventitia of the coronary 7 arteries a diabetic patient
  • Medin induces aging-related vascular dysfunction, vascular inflammation and could modulate neuroinflammation
  • An immunogen composed of medin epitope was designed to satisfy the following conditionalities: 1) specificity to medin (minimal response against parent MFGE8 so as not to disrupt its native functions or cause unintended injuries to MFGE8 expressing cells). 2) biologic relevance, 3) high immunogenicity (induction of antibody response), and 4) minimized risk of autoimmune response (T cell mediated MHC-I and MHC-II).
  • a second construct modified from the aggregation-prone C-terminal region of human medin was prepared, again substituting 2 aa’s to D-forms instead of native biologically functional L-forms, so that the longest L-aa sequence has 7 aa yet total length is 15 amino acids.
  • the second vaccine immunogen design was: KLH- C-T’-QGARN-F - GSVQFVA with T’ and F’ as D-forms.
  • the medin immunogen designed/tested (KLH-C-T’-QGARD-F’-GHIQYVA) was chosen for additional experiments. Optimum medin vaccine administration to maintain antibody response will be tested (47). Two dosing regimens will be compared: A: 0.05 mg (Time 0). 0.025 mg (Time 2 weeks, 4 weeks, 12 weeks) SQ (similar to regimen used in Table 1), or higher dose regimen B: 0. 1 mg (Time 0), 0.05 mg (Time 2 weeks, 4 weeks, 12 weeks) SQ. Medin-KLH will be in 100 pL aqueous solution given with 100 pL Freund’s adjuvant.
  • Primary outcome measures will be 1) cerebrovascular and brain parenchymal medin content, 2) cognitive function. 3) cerebrovascular function, 4) cerebrovascular and brain parenchymal inflammation. Secondary outcome measures will include serum anti-medin antibody level, neuropathology and aortic medin.
  • vascular and brain medin will be quantified using immunofluorescence (IF) or immunohistochemistry (IHC) using anti-medin antibody
  • cognitive function will be measured using novel object recognition (NOR) testing
  • cerebrovascular function will be measured using ex-vivo middle cerebral artery endothelial and smooth muscle dependent function
  • inflammation and neurovascular pathology 7 will be assessed using IF/IHC as described (7, 8, 19, 20).
  • Cognitive function Discrimination ratios of 3 variations of NOR tasks adapted from our prior work will be measured (48, 49) to evaluate short-term, long-term and working memory 7 . These are the tasks to evaluate because of the 4-day time frame for evaluation without substantial training.
  • the NOR, novel object location (NOL) and temporal order object recognition (TOR) assess short-term, long-term and working memory, respectively (50, 51).
  • Cerebrovascular function will be assessed (52, 53). Middle cerebral arteries will be cannulated and myogenic response (vessel diameter) to 0/30/60/90-mm Hg pressure (30 minutes stabilization for each) measured. The vessel will then be preconstricted with increasing doses of endothelin-1 until it reaches -60% max diameter.
  • Baseline vasoreactivity will be assessed using acetylcholine (10-9-10-4M) to assess endothelium-dependent vasodilation and NO donor (Z)-l-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-l- ium-l,2-diolate (DETA-NONOate) (10-4M) to assess smooth muscle-dependent vasodilation.
  • NO donor Z-l-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-l- ium-l,2-diolate (DETA-NONOate) (10-4M) to assess smooth muscle-dependent vasodilation.
  • Cerebrovascular and coronary medin and neurovascular pathology Cerebrovascular and coronary medin will be assessed using IHC/IF using anti-mouse medin antibodies (custom-made for us by Genscript) in the circle of Willis and leptomeningeal arteries and in hippocampal parenchymal arterioles. Quantification of % vessel area will be done using Image J. Vascular inflammation will be assessed in the same arteries using IHC/IF using antibodies against phosphorylated NFKB, IL-8, IL-6, ICAM-1 and VCAM-1.
  • Neurodegeneration will be assessed using synaptophysin IHC/IF to measure synaptic content, since synaptic loss which can represent neuronal loss as well as synaptic degeneration, is a maj or pathologic abnormality' in AD and correlates with degree of cognitive dysfunction (54, 55).
  • Neuroinflammation will be assessed using IHC/IF of activated astrocytes (glial fibrillary acidic protein GFAP) (8) and microglia (ionized calcium- binding adaptor molecule 1, Ibal).
  • mice receiving medin vaccine will develop anti-medin antibodies that will interact with newly produced medin, prevent it from aggregating into oligomers/fibrils and be cleared by the immune system.
  • Vaccinated mice will show less cerebrovascular medin and improved cognitive/cerebrovascular function versus controls. It is expected that that cerebrovascular medin burden is inversely correlated with cognitive/cerebrovascular function, and directly 7 correlated with vascular inflammation and neurovascular pathology.
  • the vaccine was designed to be immunogenic to medin and spare parent protein MFGE8 so as not to disrupt MFGE8 physiologic functions (e.g., apoptosis signaling (56)). This will be confirmed by measuring tissue MFGE8. In case MFGE8 is also reduced/impaired by vaccination, beneficial effects are expected as it was recently reported that aging-associated MFGE8 accumulation causes proin fl ammatoiy vascular remodeling which is prevented by MFGE8 knockout (57).
  • Velican D and Velican C Atherosclerotic involvement of the coronary arteries of adolescents and young adults. Atherosclerosis. 1980;36:449-60.
  • Li M Compositions and methods for selecting biallelil gene editing. 2019.
  • Monosialoganglioside-containing nanoliposomes protect against AL amyloidosis light chain induced endothelial injury through Nrf2 defense pathway. Paper presented at: 2016 Experimental Biology; 2016; San Diego CA. [00548] 54. Davies CA, Mann DM, Sumpter PQ and Yates PO. A quantitative morphometric analysis of the neuronal and synaptic content of the frontal and temporal cortex in patients with Alzheimer's disease. J Neurol Sci. 1987;78: 151-64.

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