德国科隆大学Florian Klein研究组揭示了对来自顶部中和剂的记忆B细胞进行单细胞分析，发现人巨细胞病毒(HCMV)三聚体和五聚体中存在多个易受攻击的位点。相关论文于2023年11月14日发表于国际顶尖学术期刊《免疫学》杂志上。

他们分析了来自9000个个体的四种HCMV顶层中和剂的人类B细胞反应。通过对靶向五聚体和三聚体HCMV表面复合物的记忆B细胞的单细胞分析，他们确定了共享的gH/gL亚基以及复合物特异性亚基UL128/130/131A和gO上的脆弱位点。利用高分辨率冷冻电镜，他们揭示了针对不同结合位点的抗体中和机制的结构基础。此外，他们发现了高效抗体，可以中和广谱的HCMV毒株，包括主要的临床分离株，其性能优于临床试验中使用的已知抗体。

他们的研究提供了对HCMV中和机制的深入理解，并确定了有希望的候选抗体来预防和治疗HCMV感染。

据悉，HCMV可引起胎儿、新生儿和免疫功能低下个体的严重疾病。目前，没有疫苗获得批准，治疗选择也有限。

附：英文原文

Title: Single-cell analysis of memory B cells from top neutralizers reveals multiple sites of vulnerability within HCMV Trimer and Pentamer

Author: Matthias Zehner, Mira Alt, Artem Ashurov, Jory A. Goldsmith, Rebecca Spies, Nina Weiler, Justin Lerma, Lutz Gieselmann, Dagmar Sthr, Henning Gruell, Eric P. Schultz, Christoph Kreer, Linda Schlachter, Hanna Janicki, Kerstin Laib Sampaio, Cora Stegmann, Michelle D. Nemetchek, Sabrina Dhling, Leon Ullrich, Ulf Dittmer, Oliver Witzke, Manuel Koch, Brent J. Ryckman, Ramin Lotfi, Jason S. McLellan, Adalbert Krawczyk, Christian Sinzger, Florian Klein

Issue&Volume: 2023/11/14

Abstract: Human cytomegalovirus (HCMV) can cause severe diseases in fetuses, newborns, and immunocompromisedindividuals. Currently, no vaccines are approved, and treatment options are limited.Here, we analyzed the human B cell response of four HCMV top neutralizers from a cohortof 9,000 individuals. By single-cell analyses of memory B cells targeting the pentamericand trimeric HCMV surface complexes, we identified vulnerable sites on the sharedgH/gL subunits as well as complex-specific subunits UL128/130/131A and gO. Using high-resolution cryogenic electron microscopy, we revealed the structuralbasis of the neutralization mechanisms of antibodies targeting various binding sites.Moreover, we identified highly potent antibodies that neutralized a broad spectrumof HCMV strains, including primary clinical isolates, that outperform known antibodiesused in clinical trials. Our study provides a deep understanding of the mechanismsof HCMV neutralization and identifies promising antibody candidates to prevent andtreat HCMV infection.

DOI: 10.1016/j.immuni.2023.10.009

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00449-1