ASSESSMENT OF VACCINE/MICROBICIDE COMBINATION EFFICACY IN THE MACAQUE MODEL

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表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。 开发有效的疫苗或外用化合物来预防艾滋病毒传播仍然是控制艾滋病流行的主要目标。使用异性 HIV-1 传播的非人类灵长类动物模型，我们测试了降低病毒感染性的局部杀菌剂是否可以增强部分有效的基于 T 细胞的 HIV 疫苗的功效。仅在接种疫苗的猕猴中，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攻击的情况下，才观察到猿猴/人类免疫缺陷病毒 (SHIV) 获得的显着延迟（对数秩检验；p=0.0416）。联合治疗动物的急性病毒血症峰值较低（曼-惠特尼检验；p=0.0387），病毒负荷也降低（曼-惠特尼检验；p=0.0252）。这些发现对未来采用局部杀菌剂/暴露前预防 (PrEP) 和疫苗制定艾滋病毒预防策略具有重要意义。

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.