Duke Human Vaccine Institute, Duke University, Durham, North Carolina, USA.
J Virol. 2013 Jul;87(14):7828-36. doi: 10.1128/JVI.02737-12. Epub 2013 May 8.
The detailed examination of the antibody repertoire from RV144 provides a unique template for understanding potentially protective antibody functions. Some potential immune correlates of protection were untested in the correlates analyses due to inherent assay limitations, as well as the need to keep the correlates analysis focused on a limited number of endpoints to achieve statistical power. In an RV144 pilot study, we determined that RV144 vaccination elicited antibodies that could bind infectious virions (including the vaccine strains HIV-1 CM244 and HIV-1 MN and an HIV-1 strain expressing transmitted/founder Env, B.WITO.c). Among vaccinees with the highest IgG binding antibody profile, the majority (78%) captured the infectious vaccine strain virus (CM244), while a smaller proportion of vaccinees (26%) captured HIV-1 transmitted/founder Env virus. We demonstrated that vaccine-elicited HIV-1 gp120 antibodies of multiple specificities (V3, V2, conformational C1, and gp120 conformational) mediated capture of infectious virions. Although capture of infectious HIV-1 correlated with other humoral immune responses, the extent of variation between these humoral responses and virion capture indicates that virion capture antibodies occupy unique immunological space.
详细研究 RV144 的抗体库为理解潜在保护性抗体功能提供了一个独特的模板。由于固有检测方法的限制,以及需要将相关性分析集中在有限的几个终点上以获得统计效力,因此在相关性分析中,一些潜在的免疫相关性保护因素未进行测试。在 RV144 试点研究中,我们确定 RV144 疫苗接种可引发能够结合感染性病毒粒子的抗体(包括疫苗株 HIV-1 CM244 和 HIV-1 MN 以及表达传播/原始Env 的 HIV-1 株,B.WITO.c)。在 IgG 结合抗体谱最高的疫苗接种者中,大多数(78%)捕获了具有传染性的疫苗株病毒(CM244),而一小部分疫苗接种者(26%)捕获了 HIV-1 传播/原始Env 病毒。我们证明了多种特异性的疫苗诱导的 HIV-1 gp120 抗体(V3、V2、构象 C1 和 gp120 构象)介导了感染性病毒粒子的捕获。尽管感染性 HIV-1 的捕获与其他体液免疫反应相关,但这些体液免疫反应与病毒粒子捕获之间的变化程度表明,病毒粒子捕获抗体占据了独特的免疫空间。