The long term goals of this research are to examine the immunogenicity of peptide-phospholipid complexes in stimulating a protective immune response to HIV. Our research has demonstrated that peptide-pospholipid composites can stimulate very high antibody titers when the peptides which code for both B cell and The cell epitopes are covalently linked to phosphatidylethanolamine and injected as a peptide-phospholipid composiete. These composites do not require additional adjuvates such as Freund's or alum for immunogneicity.
The specific aims of this proposal are; i) to induce neutralizing antibodies by combining the known neutralizing epitopes of HIV with known Th cell epitopes; ii) to examine the ability of peptides which describe cytolytic T cell epitope and Th cell epitopes to stimulate a CTL response and; iii) to combine those epitopes which produce the greatest amount of neutralizing antibody, CTL and T cell help into a single construct. These peptides will be synthesized as individual epitopes, repeats of the same epitope and multiple epitopes and examined in the context of peptide-phospholipid composites for stimulation of the immune response. These composites will be used of immunize mice. Antibody levels to both the peptide and intact protein (either gp120 or gp41) will be assayed by ELISA in our laboratory. Those exhibiting high titers will be assayed for neutralization of the virus at MVI in Gaithersburg, MD. Cell mediated immunity will be assayed initially at our facility for CL and positive constructs will be retested at MVI.
| Fuerst, T R; de la Cruz, V F; Bansal, G P et al. (1992) Development and analysis of recombinant BCG vector systems. AIDS Res Hum Retroviruses 8:1451-5 |
| Fuerst, T R; Stover, C K; de la Cruz, V F (1991) Development of BCG as a live recombinant vector system: potential use as an HIV vaccine. Biotechnol Ther 2:159-78 |
