Vaccines Using Synthetic Peptide-Poly IC Complexes that Elicit T-cell Responses Comparable to Live Vaccination

New vaccine technology would work with vaccines where T cells are important, such as viruses, AIDS, Cancer, Malaria, Leishmania, Hepatitis B or C, Influenza, and SARS.The unmet need is to make synthetic vaccines more like ΓÇ£liveΓÇØ vaccines. For comparison, with the flu or EBV, people get 30-50% of all T cells specific for the viral challenge, but synthetic vaccines only result in 1-2% of all T cells specific for the epitope being used.In a murine system, these modified synthetic peptides generate responses as high as 30-50% of all CD-8 T cells specific for the epitope being used.The vaccine market is a multi-billion dollar market with 2009 sales of over $20 billion from the five largest companies: Sanofi Pasteur, GlaxoSmithKline, Merck, Pfizer, and Novartis.

Peptides that are modified by the addition of either the cationic amino acids arginine (R), lysine (K), a small stretch of hydrophobic residues (e.g.,MFVMFV) or lipids (e.g., palmitic acids) become highly immunogenic, generating large numbers of antigen-specific CD8 T-lymphocytes when administered together as a mix with the immune adjuvant, polyinosinic:polycytidylic acid (Poly-IC). The modified peptides can associate via ionic bonds and/or hydrophobic interactions with Poly-IC. Because not all modified peptides associate with Poly-IC, the inventors have also developed a more general approach where the peptides can be covalently linked to poly-lysine (poly-K), and then the peptide/poly-K conjugate can associate with Poly-IC resulting in a strong immunogenic response. The efficacy of the vaccine has been demonstrated to elicit robust CD8 T-cell specific responses in a murine system.

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