Structural and Functional Studies of Experimental HIV Synthetic Peptide Immunogens

Abstract

Abstract : Work performed in this grant continues to address 2 major problems in HIV synthetic peptide vaccine development: (1) the ability of synthetic peptides to mimic conformational antibody epitopes of HIV envelope proteins and induce immune responses capable of neutralizing primary HIV isolates, and (2) the design of optimally immunogenic multivalent peptide immunogens capable of being recognized by MHC Class I and II molecules in outbred populations. In technical aim #1, intranasal immunization with HIV synthetic peptide immunogens was found to be effective for the induction of serum anti-peptide IgG antibody responses. Studies are currently being performed to determine if the qualities of the antibodies induced by intranasal immunization are different from antibodies induced by systemic immunization. Amino acid substitutions that enhanced the immunogenicity of systemically administered peptides were associated with enhanced immune responses when the peptides were administered intranasally. In technical aim #2, mutant peptides are being designed and analyzed for structure and immunogenicity in association with Aim #1. In technical aim #3, HIV synthetic peptides are being tested for their ability to bind human HLA Class I molecules.