AEGiS-11IAC: Genetic and immunologic characterization of viruses infecting MN-rgp120 vaccinated volunteers.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Genetic and immunologic characterization of viruses infecting MN-rgp120 vaccinated volunteers.

Int Conf AIDS 1996 Jul 7-12; 11:10 (abstract no. Mo.A.285)
Berman PW, Gray A, Ashby M, Eastman D, Wrin T, Vennari JA, Francis D, Gregory T, Fast P, Schwartz D, Gorse G, McElrath MJ; Genetech, Inc., South San Francisco, CA. Fax: (415) 225-2006.

OBJECTIVE: To determine whether individuals who acquired HIV-1 infections, through high risk behavior, during vaccine safety and immunogenicity studies, were infected by viruses with envelope glycoproteins that resembled the vaccine immunogen, MN-rgp 120.

METHODS: 10 of 507 adults participating in Phase I and II vaccine trials of MN-rgp 120 have become infected with HIV-1. The immune responses and virus envelope glycoproteins from 7 of the 10 infections were analyzed by ELISA and sequencing of proviral DNA. Recombinant gp120 from breakthrough viruses was prepared in CHO cells.

RESULTS: Antibodies to gp 120 were present prior to HIV-1 infection in all seven volunteers, suggesting that priming to MN-rgp 120in insufficient to provide protective immunity. Analysis of proviral sequences showed that three of seven infections resulted from viruses with typical subtype B V3 domain sequences (GPGRAF) whereas four of the infections resulted from viruses that possessed unusual V3 domain sequences (predicted to occur in less than 0.4% of subtype B infections). When the sequences of neutralizing epitopes in the V2 and C4 domain were examined, the viruses from six of the seven infections all possessed sequences that differed from the vaccine immunogen. Recombinant gp 120 was prepared from each breakthrough virus and evaluated for the ability to bind HIV-1MN neutralizing monoclonal antibodies. Our results suggest that the antigenic structure of gp 120 from the majority of breakthrough infections differed from MN-rgp 120 at neutralizing epitopes in the V2, V3, and C4 domains.

CONCLUSIONS: These studies raise the possibility that immunization with MN-rgp 120 may have prevented infection by some (MN-like), but not all, viruses during the peak of the antibody response, but failed to provide protection in the waxing or waning phases of the immune restudies raise the possibility that immunization with MN-rgp 120 may have prevented infection by some (MN-like), but not all, viruses during the peak of the antibody response, but failed to provide protection in the waxing or waning phases of the immune response. Studies with larger samples sizes will be required to determine if vaccination with MN-rgp120 has any effect on the incidence of natural infections.

Keywords: AEGIS, HIV-1, AIDS Vaccines, HIV Infections, Vaccines, Synthetic, Vaccination, Manganese, Antibodies, Monoclonal, Vaccines, Adult, immunology, virology, pathogenicity, genetics, ICA11

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MoA285