Structural and Functional Studies of Experimental HIV Synthetic Peptide Immunogens.
Annual rept. 30 Sep 95-29 Sep 96,
DUKE UNIV MEDICAL CENTER DURHAM NC
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This grant addresses 2 major problems in HIV synthetic peptide vaccine development 1 the ability of synthetic peptides to mimic conformational determinants of HIV envelope proteins, and 2 the design of optimally immunogenic multivalent peptide immunogens capable of being recognized by MllC Class I and II types of outbred populations. In Technical Aim T.A. 1, a peptide mimitope of the 48d human mab has been found that binds to fusin T cells, and in binding to human cells, ceases exposure of the 48d binding site. Immunogenic gpi2O C4-V3 peptides have been mutated based on structural predictions that improve the immunogenicity of C4-V3 peptides. New potentially neutralizing determinant peptides from HIV gpi2O and gp4i have been made and are being tested in a novel water based adjuvant strategy utilizing intranasal immunization for optimal systemic antibody response generation. In T.A.2, the 4 C4-V3 peptides from HIV MN, RF, EV9i and CANOA as well as C4 mutant peptides have been studied using NMR, their solution conformers determined, and structure-function relationships made with studies in T.A.1. In T.A.3, an assay has been developed to predict HIV peptide binding to specific HLA molecules.
- Medicine and Medical Research