A NEW APPROACH TO AIDS RESEARCH AND PREVENTION - THE USE OF GENE-MUTATED HIV-1 SIV CHIMERIC VIRUSES FOR ANTI-HIV-1 LIVE-ATTENUATED VACCINES/

The lack of a suitable animal model is a major obstacle to developing anti-HIV-1 vaccines. We successfully generated an SIVmac/HIV-1 chimeri c virus (SHIV) (designated as NM-3rN) that contains the HIV-1 env gene and is infectious to macaque monkeys, Challenging the vaccinated maca que monkeys with NM-3rN, we developed an evaluation system for anti-HI V-1 Env-targeted vaccines. For the purpose of making the vaccine, a se ries of gene-mutated SHIVs were constructed. The monkeys vaccinated wi th these SHIVs had long-term anti-virus immunities without manifesting the disease, and became resistant to a challenge inoculation with NM- 3rN. The sera from a monkey showed that, after the vaccination, the ne utralizing antibodies not only against the parental HIV-1 but also aga inst an antigenically different HIV-1 were raised. In vivo experiments confirmed that the vaccinated monkeys were protected from the challen ge inoculum of an antigenically different SHIV-MN. Vaccination of monk eys with the attenuated SHIVs showed that further gene-deletion of the SHIV resulted in less immunogenicity, Nevertheless, the attenuated SH IVs had a vaccine effect against the challenge inoculation. In additio n to specific immunities including neutralizing antibodies and cytotox ic T cells, a more complicated immune mechanism induced by live vaccin e appears to play a role in this protection. Our data suggest that the live vaccine can induce strong and wide-range immunity against HIV-1. These SHIVs should contribute to understanding the pathogenicity of A IDS and to the development of future anti-HIV-1 live vaccines for huma ns.