Delay of simian human immunodeficiency virus infection and control of viral replication in vaccinated macaques challenged in the presence of a topical microbicide.

摘要

OBJECTIVE: Development of an effective vaccine or topical compound to prevent HIV transmission remains a major goal for control of the AIDS pandemic. Using a nonhuman primate model of heterosexual HIV-1 transmission, we tested whether a topical microbicide that reduces viral infectivity can potentiate the efficacy of a T-cell-based HIV vaccine. DESIGN: A DNA prime and rAd5 virus boost vaccination strategy was employed, and a topical microbicide against the HIV nucleocapsid protein was used. To rigorously test the combination hypothesis, the vaccine constructs contained only two transgenes and the topical microbicide inhibitor was used at a suboptimal dose. Vaccinees were exposed in the absence and presence of the topical microbicide to repeated vaginal R5 simian human immunodeficiency virus (SHIV)(SF162P3) challenge at an escalating dose to more closely mimic high-risk exposure of women to HIV. METHODS: Infection status was determined by PCR. Antiviral immune responses were evaluated by gp120 ELISA and intracellular cytokine staining. RESULTS: A significant delay in SHIV acquisition (log-rank test; P = 0.0416) was seen only in vaccinated macaques that were repeatedly challenged in the presence of the topical microbicide. Peak acute viremia was lower (Mann-Whitney test; P = 0.0387) and viral burden was also reduced (Mann-Whitney test; P = 0.0252) in the combination-treated animals. CONCLUSION: The combined use of a topical microbicide to lower the initial viral seeding/spread and a T-cell-based vaccine to immunologically contain the early virological events of mucosal transmission holds promise as a preventive approach to control the spread of the AIDS epidemic.