Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA.
Cell. 2019 Jul 25;178(3):567-584.e19. doi: 10.1016/j.cell.2019.06.030.
The vaccine-mediated elicitation of antibodies (Abs) capable of neutralizing diverse HIV-1 strains has been a long-standing goal. To understand how broadly neutralizing antibodies (bNAbs) can be elicited, we identified, characterized, and tracked five neutralizing Ab lineages targeting the HIV-1-fusion peptide (FP) in vaccinated macaques over time. Genetic and structural analyses revealed two of these lineages to belong to a reproducible class capable of neutralizing up to 59% of 208 diverse viral strains. B cell analysis indicated each of the five lineages to have been initiated and expanded by FP-carrier priming, with envelope (Env)-trimer boosts inducing cross-reactive neutralization. These Abs had binding-energy hotspots focused on FP, whereas several FP-directed Abs induced by immunization with Env trimer-only were less FP-focused and less broadly neutralizing. Priming with a conserved subregion, such as FP, can thus induce Abs with binding-energy hotspots coincident with the target subregion and capable of broad neutralization.
诱导能够中和多种 HIV-1 毒株的抗体（Abs）一直是一个长期目标。为了了解如何能够诱导出广泛中和抗体（bNAbs），我们在接种疫苗的猕猴中鉴定、表征和跟踪了针对 HIV-1-融合肽（FP）的五个中和 Ab 谱系，随着时间的推移。遗传和结构分析表明，这两个谱系中的两个属于可重复的类别，能够中和多达 59%的 208 种不同的病毒株。B 细胞分析表明，这五个谱系中的每一个都通过 FP 载体引发和扩增，包膜（Env）三聚体增强诱导交叉反应性中和。这些 Ab 的结合能热点集中在 FP 上，而免疫接种仅用 Env 三聚体诱导的几个 FP 定向 Ab 则不那么集中在 FP 上，也不那么广泛中和。因此，用保守的亚区域（如 FP）进行引发，可以诱导出与目标亚区域具有相同结合能热点的 Ab，并且能够进行广泛中和。
