PROTECTION OF MONKEYS VACCINATED WITH VPR-DEFECTIVE AND OR NEF-DEFECTIVE SIMIAN IMMUNODEFICIENCY VIRUS-STRAIN MAC HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 CHIMERIC VIRUSES - A POTENTIAL CANDIDATE LIVE-ATTENUATED HUMAN AIDS VACCINE/

Two simian immunodeficiency virus strain mac (SIVmac)/human immunodefi ciency virus type 1 (HIV-1) chimeric viruses (SHIVs), designated NM-3 and NM-3n, with env derived from HIV-1 and defective vpr (plus defecti ve nef for NM-3), were inoculated into seven macaques. These macaques were transiently or persistently infected and most of them produced lo ng-lasting neutralizing antibodies and Env-specific killer T cells to HIV-1 with no AIDS-like symptoms. When they were challenged with anoth er SHIV with intact vpr and nef (designated NM-3rN), all were protecte d as judged by virus recovery, DNA detection by PCR and antibody respo nses. Anti-HIV-1 Env-specific killer T cells were considered to have p layed a major role in this protection, but a non-specific defence mech anism as well as specific immunity also appeared to be involved. Thus, these two non-pathogenic SHIVs induced long-lasting protective immuni ties in macaques, suggesting the possibility of gene-defective SHIVs a s attenuated live vaccines for human use.