AEGiS-11IAC: Protection from HIV-1 challenge in chimpanzees by immunization with an HIV-1 canarypox virus recombinant.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Protection from HIV-1 challenge in chimpanzees by immunization with an HIV-1 canarypox virus recombinant.

Int Conf AIDS 1996 Jul 7-12; 11:10 (abstract no. We.A.280)
van der Ryst E, Fultz PN, Tartaglia J, Barre-Sinoussi F, Paoletti E, Nara P, Meignier B, Blondeau C, Muchmore E, Girard M; Unite de Virologie Moleculaire, Institut Pasteur, Paris, France. Fax: 33-1-40613045. E-mail: elna@pasteur.fr.

OBJECTIVE: To determine whether chimpanzees could be protected from infection with cell-associated HIV-1 by immunization with a live recombinant HIV-1 canarypox virus.

METHODS: Two adult male chimpanzees were immunized at months 0, 1, 5, 9 and 11 with 4x108 plaque-forming units of ALVAC HIV-1 vCP250, a recombinant canarypox virus expressing the HIV-1 LAI gp120/TM, gag and protease genes. The animals and a naive control chimpanzee were challenged one month after the last boost with cell-associated HIV-1 in the form of 6x105 HIV-1 IIIB(LAI)-infected peripheral blood mononuclear cells (PBMC). Blood samples were collected at regular intervals for analysis of immune responses to HIV-1 antigens by immunoblot and enzyme immunoassays. A syncytium-inhibition assay was used to test for neutralizing antibodies. After virus challenge, the animals were monitored for the presence of virus in PBMC and the development of an anamnestic antibody response.

RESULTS: PBMC from one immunized and the control animal were virus positive, and increases in antibody titers were noted 4-6 weeks after challenge. The other immunized animal appeared to be protected from challenge and remained virus negative with a decrease in antibody titers. Of interest was the observation that the neutralizing antibody titer of the infected animal was 32, whereas that of the protected animal was 128.

CONCLUSIONS: These results confirm those of previous studies suggesting a correlation between neutralizing antibody titers and protection in the chimpanzee model. They also show that a live recombinant HIV-1 canarypox virus can induce protective neutralizing antibody titers after repeated immunization with high doses of virus. The protected animal will be boosted again and challenged with an heterologous HIV-1 strain from the same clade (B) to test whether intraclade protection is possible.

Keywords: AEGIS, HIV-1, Pan troglodytes, AIDS Vaccines, HIV Antigens, Immunization, Giant Cells, Immunoenzyme Techniques, Canarypox virus, Immunoblotting, ALVAC-HIV-1 vCP250, Animal, Adult, Male, ICA11

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WeA280