AEGiS-07IAC: HIV-1 major neutralizing determinant exposed on HBsAG particles is immunogenic in primates.

7th International AIDS Conference

Florence, Italy — June 16-21, 1991

HIV-1 major neutralizing determinant exposed on HBsAG particles is immunogenic in primates.

Int Conf AIDS 1991 Jun 16-21; 7:88 (abstract no. F.A.4)
Schlienger K, Michel ML, Mancini M, Dormont D, Riviere Y, Tiollais P; Unite de Recombinaison et Expression Genetique, Paris, France

OBJECTIVE: The HIV-1 major neutralizing determinant is contained within a disulfide loop located in the envelope gp 120 third variable domain (V3 loop). To increase its immunogenic potential, we have exposed this epitope (HIV-1 Bru strain) at the surface of a highly antigenic structure, the hepatitis B surface antigen (HBsAg). Then we studied the humoral and T cell response profile in nonhuman primates immunized with these hybrid recombinant particles (V3/HBsAg).

METHODS: Six rhesus monkeys divided in 2 groups received 2 intradermic injections at 1 month interval and 1 boost 8 months later of either V3/HBsAg or non hybrid recombinant particles, i.e. HBsAg (1 control animal per group). Immunization was potentiated with alum in one group and Syntex adjuvant in the other one. Serum antibody responses were determined by Western blot, ELISA and neutralization assays, and evaluated for antibody dependent cellular cytotoxicity (ADCC). T cell in vitro proliferative responses to a panel of antigens were assessed as well as MHC dependent cellular cytotoxicity (CTL).

RESULTS: Immunized monkeys developed persistent antibodies and T cell proliferative response against both parts of the fusion protein (HBsAg and HIV-1). Neutralizing antibodies were detectable in 2 macaques after boosting and this response will be further investigated. ADCC was also found after boosting, when cells infected by gp160 (HIV-1 Bru) expressing recombinant vaccinia viruses were used as targets. Finally, the two groups treated with different adjuvants did not show any difference.

CONCLUSIONS: Since there is an overlap between populations at risk from hepatitis B virus (HBV) and HIV, HBsAg recombinant particles may be relevant carriers for HIV-1 major epitopes, as they were shown to generate neutralizing antibodies, ADCC and T cell proliferative response.

Keywords: AEGIS, Hepatitis B Surface Antigens, HIV-1, HIV Antibodies, HIV Envelope Protein gp120, HIV Envelope Protein gp160, HIV Antigens, Hepatitis B Virus, HIV Envelope Protein gp41, Immunization, Antibody-Dependent Cell Cytotoxicity, T-Lymphocytes, Vaccinia virus, Primates, Blotting, Western, HIV, Epitopes, Animal, In Vitro, immunology, ICA7
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