美国约翰霍普金斯大学医学院Justin R. Bailey等研究人员合作发现，人类广谱中和抗体对不同E2表位的趋同演化和靶向作用与HCV清除率有关。相关论文于2024年3月21日在线发表在《免疫》杂志上。

研究人员表示，血清中广泛中和抗体（bNAb）的早期出现与丙型肝炎病毒（HCV）的自发清除有关，但迄今为止，大多数bNAb都是从慢性感染的供体中分离出来的。这些bNAb大多使用V_H1-69基因片段，靶向包膜糖蛋白E2前层。

研究人员对一名自发清除了多次HCV感染的精英中和者进行了纵向B细胞受体（BCR）谱系分析。研究人员分离了10680个E2反应性B细胞，进行了BCR测序，确定了单克隆B细胞培养物的特征，并分离出了bNAb。与在慢性感染供体中看到的情况不同，这些bNAb使用了多种VH基因，并针对至少三个不同的E2抗原位点，包括以前认为的非中和位点。不同的前层反应性bNAb谱系趋同演化，获得了广度增强的体细胞突变。这些研究结果表明，HCV清除相关的bNAb具有基因多样性，并能结合不同的抗原位点，这些位点应成为疫苗诱导的bNAb的靶点。

附：英文原文

Title: Convergent evolution and targeting of diverse E2 epitopes by human broadly neutralizing antibodies are associated with HCV clearance

Author: Clinton O. Ogega, Nicole E. Skinner, Marta V. Schoenle, Xander E. Wilcox, Nicole Frumento, Desiree A. Wright, Harry T. Paul, Ariadne Sinnis-Bourozikas, Kaitlyn E. Clark, Alexis Figueroa, Pamela J. Bjorkman, Stuart C. Ray, Andrew I. Flyak, Justin R. Bailey

Issue&Volume: 2024-03-21

Abstract: The early appearance of broadly neutralizing antibodies (bNAbs) in serum is associatedwith spontaneous hepatitis C virus (HCV) clearance, but to date, the majority of bNAbshave been isolated from chronically infected donors. Most of these bNAbs use the VH1-69 gene segment and target the envelope glycoprotein E2 front layer. Here, we performedlongitudinal B cell receptor (BCR) repertoire analysis on an elite neutralizer whospontaneously cleared multiple HCV infections. We isolated 10,680 E2-reactive B cells,performed BCR sequencing, characterized monoclonal B cell cultures, and isolated bNAbs.In contrast to what has been seen in chronically infected donors, the bNAbs used avariety of VH genes and targeted at least three distinct E2 antigenic sites, including sites previouslythought to be non-neutralizing. Diverse front-layer-reactive bNAb lineages evolvedconvergently, acquiring breadth-enhancing somatic mutations. These findings demonstratethat HCV clearance-associated bNAbs are genetically diverse and bind distinct antigenicsites that should be the target of vaccine-induced bNAbs.

DOI: 10.1016/j.immuni.2024.03.001

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00097-9