SIV/HIV-1 chimeric viruses having HIV-1 env gene : A new animal model and a candidate for attenuated live vaccine

In order to generate an HIV-1, which is infectious to and induces AIDS-like disease in monkeys, an SIVmac/HIV-1 chimeric virus, designated NM-3rN, which was replication-competent in monkeys, was constructed by recombination between HIV-1 and SIV mac genomes. The NM-3rN enabled to evaluate the efficacy of HIV-1 Env-directed vaccines using macaque monkeys instead of chimpanzees, because NM-3rN had HIV-1 derived Env. Other NM-3rN-derivative chimeric viruses, designated NM-3 and NM-3n, which had defective vpr (plus nef for NM-3) genes, induced long-term persistent infection in monkeys having long-lasting humoral and cell-mediated immune reactions without manifesting the disease. The challenge inoculation with NM-3rN to these defective chimeric virus-infected monkeys resulted in protection. Furthermore, these protected monkeys were also resistant to challenge with another chimeric virus having different antigenicity in V3 loop from that of NM-3 and NM-3n. These results indicate that SIV/HIV-1 chimeric viruses may be a potential candidate for development of anti-AIDS live attenuated vaccines.