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Support of Study Entitled, "Conformationally Restricted Synthetic Aids Vaccine"
Annual rept. 1 Jul 1997-30 Jun 1998
SCRIPPS RESEARCH INST LA JOLLA CA
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Our proposal was directed to the identification of synthetic peptide mimetics corresponding to neutralizing epitopes recognized by IgG1b12 and MAb 58.2. Herein, we report recent results on MAb 58.2 which provides important new information regarding methods and outcomes for synthetic vaccines as well as specific information about the role that conformation plays in neutralizing immune responses to the V3 epitope. MAb 58.2 displays broad reactivity against Clade B gp120s from primary isolates. It weakly neutralizes a cloned macrophage-tropic primary isolate, JR-CSF. We identified a constrained V-3 loop mimetic that binds 1,000 times better to MAb 58.2 than the corresponding linear peptide. Rabbit polyclonal antibodies to the constrained peptide but not the linear peptide bind rgp120 MN. Furthermore, the polyclonal immune response to a constrained V3 peptide mimics the conformational preference and neutralizing activity of MAb 58.2. HIV-1 neutralization correlates with conformational preference and affinity for gp120. These results and others presented in the report establish beyond doubt the remarkable improvements in antigenicity and immunogenicity of constrained peptides compared to linear peptides.
APPROVED FOR PUBLIC RELEASE