Merck Vaccines, West Point, Pennsylvania, USA.
Curr Opin HIV AIDS. 2010 Sep;5(5):377-85. doi: 10.1097/COH.0b013e32833d2e19.
To consider how nonhuman primate (NHP) model systems can best contribute to HIV vaccine development.
We review the traditional roles of NHP model systems in vaccine development and compare this with how NHP models have been used in HIV vaccine research and development. Comparisons of the immune responses elicited by cellular immune response-inducing vaccines in macaques and humans illustrate the value of primate studies for the relative ranking of HIV vaccine concepts for their likely immunogenicity in humans. The unusual structures (e.g. long complementarity-determining regions) of known broadly neutralizing HIV antibodies (bNAbs) suggest that it is critical to test candidate env immunogens in NHPs, whose germline antibody repertoires resemble those of humans. Recent clinical efficacy trial results question the utility of existing NHP challenge models in predicting HIV vaccine efficacy in humans, and highlight the need to further develop models in which acquisition of infection can be reliably evaluated. When evaluated in models using low virus dose challenges that better approximate human sexual exposure to HIV - some vaccine and passive NAb interventions appear to protect against acquisition of infection.
NHP models have important roles in the preclinical evaluation, optimization, and ranking of novel HIV immunogens. The apparent vaccine efficacy observed using low virus dose challenge models provides an opportunity to investigate the correlates of protection.
探讨非人类灵长类动物（NHP）模型系统如何能为 HIV 疫苗开发做出最大贡献。
我们回顾了 NHP 模型系统在疫苗开发中的传统作用，并将其与 NHP 模型在 HIV 疫苗研究和开发中的应用进行了比较。比较猕猴和人类中细胞免疫反应诱导疫苗引起的免疫反应，说明了灵长类动物研究对于相对评估 HIV 疫苗概念的价值，这些概念可能对人类的免疫原性具有较高的可能性。已知广泛中和 HIV 抗体（bNAb）的不寻常结构（例如长互补决定区）表明，在 NHP 中测试候选 env 免疫原至关重要，因为 NHP 的种系抗体库与人类相似。最近的临床疗效试验结果质疑了现有 NHP 挑战模型在预测人类 HIV 疫苗疗效方面的实用性，并强调需要进一步开发可以可靠评估感染获得的模型。当使用更接近人类性接触 HIV 的低病毒剂量挑战模型进行评估时 - 一些疫苗和被动 NAb 干预措施似乎可以预防感染的获得。
NHP 模型在新型 HIV 免疫原的临床前评估、优化和分级中具有重要作用。使用低病毒剂量挑战模型观察到的明显疫苗疗效提供了一个机会来研究保护相关性。
