Live, attenuated simian immunodeficiency virus vaccines elicit potent resistance against a challenge with a human immunodeficiency virus type 1 chimeric virus

Three rhesus macaques, previously immunized with SIVD3 or SIVD2, each an attenuated derivative of SIVmac239, and two naive monkeys were challenged with 30,000 50 % tissue culture infective doses of SHIV, an SIV/human immunodeficiency virus type 1 (HIV-1) chimeric virus bearing the dual-tropic envelope of HIV-1DH12. By several criteria, including virus isolation, serological assays, and PCR (both DNA and reverse transcriptase), SHIV levels were reduced to barely detectable levels in the circulating blood of vaccinated animals. The resistant SIV-vaccinated macaques had no preexisting neutralizing antibodies directed against SHIV, nor did they produce neutralizing antibodies at any time over a 14-month observation period following SHIV challenge. Interestingly, SIV sequences, derived from the vaccine, could be amplified from numerous tissue samples collected at the conclusion of the experiment, 60 weeks postchallenge, but SHIV-specific sequences (viz., HIV-1 env) could not. These results demonstrate that live attenuated SIV vaccines provide strong long-term protection even against challenge strains with highly divergent envelope sequences. The last decade has witnessed impressive advances in our knowledge of human immunodeficiency virus (HIV-1) biology and has resulted in the discovery and clinical application of potent antiviral agents that target virus-encoded proteins. I