ASSESSMENT OF VACCINE/MICROBICIDE COMBINATION EFFICACY IN THE MACAQUE MODEL

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心赠款提供。次级项目的主要支助 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 表示子项目使用的中心基础设施的估计数量， NCRR赠款不直接向子项目或子项目工作人员提供资金。 开发有效的疫苗或局部化合物以预防HIV传播仍然是控制艾滋病流行的主要目标。使用异性HIV-1传播的非人灵长类动物模型，我们测试了降低病毒感染性的局部杀微生物剂是否可以增强部分有效的基于T细胞的HIV疫苗的功效。猴/人类免疫缺陷病毒（SHIV）获得的显著延迟（对数秩检验; p=0.0416）仅见于在存在由HIV核衣壳蛋白抑制剂组成的杀微生物剂的情况下反复挑战的接种猕猴中。联合给药动物的急性病毒血症峰值较低（Mann-Whitney检验; p=0.0387），病毒负荷也降低（Mann-Whitney检验; p=0.0252）。这些发现对未来采用局部杀微生物剂/暴露前预防（PrEP）和疫苗的艾滋病毒预防策略的发展具有影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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 partially effective T-cell-based HIV vaccine. A significant delay in simian/human immunodeficiency virus (SHIV) acquisition (Log-rank test; p=0.0416) was seen only in vaccinated macaques that were repeatedly challenged in the presence of a microbicide comprised of an HIV nucleocapsid protein inhibitor. 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. These findings have implications for future development of HIV prevention strategies employing topical microbicides/pre-exposure prophylaxis (PrEP) and vaccines.