HIGH-TITER IMMUNE-RESPONSES ELICITED BY RECOMBINANT VACCINIA VIRUS PRIMING AND PARTICLE BOOSTING ARE INEFFECTIVE IN PREVENTING VIRULENT SIVINFECTION

Eighteen rhesus monkeys were vaccinated with recombinant vaccinia viru ses expressing SIVmac antigens in 3 separate rounds of experiments. Tw elve of the monkeys were primed with a trivalent vaccinia virus recomb inant expressing Gag, Pol, and Env polypeptides that can assemble into SIV pseudovirion particles and boosted with SIV particles in adjuvant . Four of the monkeys were primed with different vaccinia virus recomb inants expressing env or gag + env followed by SIV particle boosts; tw o received vaccinia virus recombinants alone (env or env + gag). Despi te the induction of vigorous immune responses, 17 of 18 rhesus monkeys became infected on challenge with a low dose of virulent SIVmac. The single protected animal was one of three challenged with homologous cl oned SIV exactly matched to the clone used for construction of trivale nt vaccinia virus recombinant and particles. Vaccination may have dimi nished SIV burdens and rates of CD4(+) cell declines in some of the an imals, but vaccinated/challenged/infected animals eventually developed fatal disease similar to control animals. These results highlight the extreme difficulty in achieving vaccine protection against virulent S IVmac infection even under idealized laboratory conditions.