美国斯克里普斯研究所Facundo D. Batista、Shane Crotty和William R. Schief研究组合作提出了一种广泛中和抗体反应的通用艾滋病毒疫苗设计策略。 相关论文11月1日发表于国际学术期刊《科学》。

利用超深度人类抗体测序数据，研究人员鉴定了与抗体重链互补决定区3(HCDR3)相接触的广泛中和抗体(bnAb)的多种潜在抗体前体。 随后，研究人员构建了基于HIV包膜三聚体的免疫原，该免疫原可引发了小鼠模型中罕见的bnAb前体B细胞应答，并且在离体筛选中结合了一系列潜在bnAb前体人类天然B细胞。

研究人员利用数据库指导的生殖系靶向筛选方法为优化HIV bnAb的筛选提供了基础，并且该方法还可以利用来自其他病原体的HCDR3优势抗体。

据介绍，研发疫苗诱导的针对人免疫缺陷病毒(HIV)的广泛中和抗体(bnAb)仍然是一项重大挑战。靶向生殖细胞的免疫原有望产生某些类bnAb。 但是对于大多数bnAb而言，其高度依赖抗体重链互补决定区3是主要障碍。

附：英文原文

Title: A generalized HIV vaccine design strategy for priming of broadly neutralizing antibody responses

Author: Jon M. Steichen, Ying-Cing Lin, Colin Havenar-Daughton, Simone Pecetta, Gabriel Ozorowski, Jordan R. Willis, Laura Toy, Devin Sok, Alessia Liguori, Sven Kratochvil, Jonathan L. Torres, Oleksandr Kalyuzhniy, Eleonora Melzi, Daniel W. Kulp, Sebastian Raemisch, Xiaozhen Hu, Steffen M. Bernard, Erik Georgeson, Nicole Phelps, Yumiko Adachi, Michael Kubitz, Elise Landais, Jeffrey Umotoy, Amanda Robinson, Bryan Briney, Ian A. Wilson, Dennis R. Burton, Andrew B. Ward, Shane Crotty, Facundo D. Batista, William R. Schief

Issue&Volume: 2019/10/31

Abstract: Vaccine induction of broadly neutralizing antibodies (bnAbs) to human immunodeficiency virus (HIV) remains a major challenge. Germline-targeting immunogens hold promise for initiating the induction of certain bnAb classes; yet for most bnAbs, a strong dependence on antibody heavy chain complementarity determining region 3 (HCDR3) is a major barrier. Exploiting ultra-deep human antibody sequencing data, we identified a diverse set of potential antibody precursors for a bnAb with dominant HCDR3 contacts. We then developed HIV envelope trimer-based immunogens that primed responses from rare bnAb-precursor B cells in a mouse model, and in ex-vivo screens bound a range of potential bnAb-precursor human naive B cells. Our repertoire-guided germline-targeting approach provides a framework for priming the induction of many HIV bnAbs, and could be applied to most HCDR3-dominant antibodies from other pathogens.

DOI: 10.1126/science.aax4380

Source: https://science.sciencemag.org/content/early/2019/10/30/science.aax4380