HIV Vaccines Based on Novel MULV-HIV Fusion Proteins
Annual rept. 26 June 96-25 June 97
PUBLIC HEALTH RESEARCH INST OF THE CITY OF NEW YORK INC
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We have continued our efforts to develop an effective HIV-1 vaccine based on the V1JV2 domain of gp120. Studies with human sera and with antibodies isolated from immunized animals have shown that the VlV2 domain contains highly conserved epitopes that can act as potent neutralizing targets for a broad range of primary HIV-1 isolates. We have prepared a prototype immunogen, based on the Case-A2 isolate, that contains the dade B V2 consensus sequence, and have shown that this antigen induces highly crossreactive anti-VlV2 antibodies in both rats and macaques, and that specific fractions of the rat antibodies possess potent cross-neutralizing activity. We are continuing to analyze this immunogen in both the rat and macaque models, and we expect to further analyze the humoral responses to immunization with this protein, including the isolation of monoclonal antibodies against various epitopes in the V 1V2 domain. Our goal during the coming year is to more fully characterize the epitopes mediating the potent neutralization, and to modify the immunogen so that those epitopes are presented more specifically and efficiently. The macaque immunizations will provide sufficient amounts of antibodies for full characterization, and will also allow challenge studies to be performed with appropriate SHIV strains.
- Medicine and Medical Research