AEGiS-11IAC: Immunization with an HIV-1 canarypox virus recombinant confers protection against genital HIV-1 challenge in chimpanzees.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Immunization with an HIV-1 canarypox virus recombinant confers protection against genital HIV-1 challenge in chimpanzees.

Int Conf AIDS 1996 Jul 7-12; 11:13 (abstract no. We.A.393)
Girard M, Barre-Sinoussi F, Tartaglia J, van der Ryst E, Paoletti E, Nara P, Meignier B, Blondeau C, Pillot J, Mahoney J, Fultz PN; Unite de Virologie Moleculaire, Institut Pasteur, Paris, France. Fax: 33 1 40 61 30 45. E-mail: Elna@pasteur.Fr.

OBJECTIVE: To determine whether female chimpanzees could be protected from genital infection with HIV-1 after parenteral and/or mucosal immunization with a recombinant HIV-1 canarypox virus and to compare the oro-nasal and recto-vaginal immunization routes.

METHODS: Five adult female chimpanzees were immunized at 0, 2, 6, 13 and 17 months with 4x108 plaque-forming units (pfu) of ALVAC-HIV-1 vCP250, a recombinant canarypox virus expressing the HIV-1 LAI gp120/TM, gag and protease genes. Two animals were immunized by the intramuscular (i.m.), cervico-vaginal and rectal routes (1/3 dose each); two animals by the i.m., nasal and oral routes; and the fifth animal by the i.m. route only. Four of the immunized animals, and a naive control female were challenged one month after the last boost with 2500 50% tissue culture infectious doses of a chimpanzee-passaged stock of HIV-1 LAV(LAI) inoculated at the cervical os. Blood samples were collected regularly, and immune responses to HIV-1 antigens evaluated by immunoblot and enzyme immunoassays. A syncytium inhibition assay was used to test for neutralizing antibodies. Mucosal secretions were also tested for secretory antibodies. After challenge the animals were monitored for the presence of virus in peripheral blood mononuclear cells (PBMC) and development of anamnestic antibody responses.

RESULTS: The control animal became infected, as shown by the isolation of virus from PBMC and the development of an HIV-1-specific antibody response. All four vaccinated animals that were challenged remained uninfected, despite the presence of low levels of HIV-1-specific serum and secretory antibodies at time of challenge, and low levels of neutralizing antibodies (titers below less than 32).

CONCLUSIONS: Female chimpanzees can be protected from vaginal challenge with HIV-1 by repeated mucosal and systemic immunization with a live recombinant canarypox virus. The results suggest that neutralizing antibodies may be less important for protection from mucosal infection than from intravenous challenge.

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

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