Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM) and University of Montreal, Montreal, QC H2X 0A9, Canada.
Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), La Jolla, CA 92037, USA.
Viruses. 2018 Jun 19;10(6):336. doi: 10.3390/v10060336.
Passive administration of broadly neutralizing antibodies (bNAbs) capable of recognizing a broad range of viral strains to non-human primates has led to protection from infection with chimeric SIV/HIV virus (SHIV). This data suggests that generating protective antibody responses could be an effective strategy for an HIV vaccine. However, classic vaccine approaches have failed so far to induce such protective antibodies in HIV vaccine trials. HIV-specific bNAbs identified in natural infection show high levels of somatic hypermutations, demonstrating that they underwent extensive affinity maturation. It is likely that to gain ability to recognize diverse viral strains, vaccine-induced humoral responses will also require complex, iterative maturation. T follicular helper cells (Tfh) are a specialized CD4+ T cell subset that provides help to B cells in the germinal center for the generation of high-affinity and long-lasting humoral responses. It is therefore probable that the quality and quantity of Tfh responses upon vaccination will impact development of bNAbs. Here, we review studies that advanced our understanding of Tfh differentiation, function and regulation. We discuss correlates of Tfh responses and bNAb development in natural HIV infection. Finally, we highlight recent strategies to optimize Tfh responses upon vaccination and their impact on prophylactic HIV vaccine research.
被动给予能够识别广泛病毒株的广泛中和抗体（bnAbs）可使非人类灵长类动物免受嵌合 SIV/HIV 病毒（SHIV）感染。这些数据表明，产生保护性抗体反应可能是 HIV 疫苗的有效策略。然而，经典疫苗方法在 HIV 疫苗试验中迄今为止未能诱导出这种保护性抗体。在自然感染中发现的 HIV 特异性 bnAbs 显示出高水平的体细胞超突变，表明它们经历了广泛的亲和力成熟。为了获得识别多种病毒株的能力，疫苗诱导的体液反应也可能需要复杂的、迭代的成熟。滤泡辅助性 T 细胞（Tfh）是一种特殊的 CD4+T 细胞亚群，它为生发中心的 B 细胞提供帮助，以产生高亲和力和持久的体液反应。因此，接种疫苗后 Tfh 反应的质量和数量很可能会影响 bnAb 的产生。在这里，我们综述了一些研究，这些研究增进了我们对 Tfh 分化、功能和调节的理解。我们讨论了 Tfh 反应与自然 HIV 感染中 bnAb 发展的相关性。最后，我们强调了最近优化接种疫苗后 Tfh 反应的策略及其对预防性 HIV 疫苗研究的影响。
