7th International AIDS Conference Florence, Italy — June 16-21, 1991

Int Conf AIDS 1991 Jun 16-21; 7:27 (abstract no. M.A.24)
Mills KH, Stott EJ, Chan WL, Taffs LF, Cranage M, Greenaway P, Thiriart C, DeWilde M, Bruck C, Page M, et al; NIBSC, Potters Bar, Herts., UK

OBJECTIVE: To assess the ability of SIV vaccines to generate humoral and cell-mediated immunity and to protect against challenge in an SIV macaque model.

METHODS: Macaques were immunized with 4 doses of inactivated whole virus or recombinant SIV proteins. Humoral immune responses were tested by ELISA, immunoblots, RIPA and neutralization assays, cellular responses by proliferation, cytotoxicity and lymphokine release assays. Vaccinated and control animals were challenged with 10 MID50 SIVmac251 32H isolate and tested for infectivity by virus isolation and PCR analysis.

RESULTS: Formalin inactivated SIVmac251 32H in syntex adjuvant formulation (SAF-1) protected 100% animals (groups of 4) against homologous or heterologous (SIVdelta, provided by M. Murphey-Corb) SIV challenge but not HIV-2 (HIV-2 SBL 6669, provided by G. Biberfeld). BPL-inactivated SIVmac BK28 in Freunds adjuvant protected 3 of 3 animals against SIVmac 32H challenge. A recombinant SIV gag protein expressed in yeast as p27:Ty-virus-like-particles (provided by British Biotechnology, Oxford) failed to protect against SIV challenge or to prime for anamnestic anti-env antibody response, in the presence of gag-specific T helper cell responses. An SIVmac BK28 env/gag recombinant vaccine, comprising gp150 expressed in vaccinia virus and p57 expressed in baculovirus, in SAF-1 induced consistent anti-SIV T cell responses and high levels of neutralizing antibodies. The outcome of SIV challenge will be reported.

CONCLUSIONS: Protection against homologous or heterologous challenge is possible using inactivated SIV in different adjuvants. The immunogenicity and efficacy studies with the inactivated virus and recombinant SIV proteins may help in the elucidation of the mechanism of protective immunity and in HIV vaccine design.

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