Macaque studies of vaccine and microbicide combinations for preventing HIV-1 sexual transmission
Macaque studies of vaccine and microbicide combinations for preventing HIV-1 sexual transmission
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DOI：
10.1073/pnas.1203183109
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发表时间：
2012-05-29
影响因子：
11.1
通讯作者：
Moore, John P.
中科院分区：
文献类型：
--
作者：
Barouch, Dan H.;Klasse, Per Johan;Moore, John P.
接种疫苗和使用阴道杀微生物剂传统上被认为是预防妇女通过性行为感染HIV-1的独立方法。这两种技术在猕猴模型中都是有效的，在临床试验中观察到的效果有限。在这里，我们讨论了疫苗和杀微生物剂是否可以一起使用，以提供加强保护，对病毒的攻击恒河猴。在两个单独的实验中，四组动物接种了T细胞为基础的腺病毒（Ad）载体的疫苗，旨在减少感染后病毒载量和/或部分有效剂量的阴道杀微生物剂，旨在阻断感染的高剂量阴道挑战SIVmac 251或SHIV-162 P3。在第一项研究中，仅有的两只受保护动物是在SIVmac 251攻击之前接受与融合抑制剂T-1249组合的Ad 26/Ad 5 HVR 48疫苗载体作为阴道杀微生物剂的组中。在第二项研究中，接种Ad 35/Ad 26载体联合CCR 5抑制剂马拉韦罗作为阴道杀微生物剂，导致SHIV-SF 162 P3攻击后感染和感染后病毒载量的显著减少。正如预期的那样，疫苗本身降低了病毒载量，但没有获得效应，而杀微生物剂具有部分获得效应，但对病毒载量的影响最小。对于这两种保护效果的措施，疫苗-杀微生物剂组合与对照组的差异大于单独干预。总的来说，数据表明，疫苗和杀微生物剂是互补的技术，一起使用比单独使用更好地保护。
Vaccination and the application of a vaginal microbicide have traditionally been considered independent methods to prevent the sexual transmission of HIV-1 to women. Both techniques can be effective in macaque models, and limited efficacy has been observed in clinical trials for each. Here, we have addressed whether vaccines and microbicides can be used together to provide reinforced protection against virus challenge of rhesus macaques. In two separate experiments, four groups of animals were vaccinated with a T-cell-based adenovirus (Ad) vectored vaccine aimed at reducing postinfection viral loads and/or a partially effective dose of a vaginal microbicide aimed at blocking infection of a high-dose vaginal challenge with SIVmac251 or SHIV-162P3. In the first study, the only two protected animals were in the group that received Ad26/Ad5HVR48 vaccine vectors combined with the fusion inhibitor T-1249 as the vaginal microbicide before SIVmac251 challenge. In the second study, vaccination with Ad35/Ad26 vectors combined with the CCR5 inhibitor maraviroc as the vaginal microbicide led to significant reductions of both acquisition of infection and postinfection viral loads following SHIV-SF162P3 challenge. As expected, the vaccine by itself reduced viral loads but had no acquisition effect, whereas the microbicide had a partial acquisition effect but minimal impact on viral loads. For both measures of protective efficacy, the vaccine-microbicide combination differed more from controls than did either separate intervention. Overall, the data suggest that vaccines and microbicides are complementary techniques that may protect better when used together than separately.