美国芝加哥大学Patrick C. Wilson团队提出了接种嵌合流感病毒血凝素后，B细胞长时间趋同到不同的广泛反应性表位。相关论文于2025年3月24日发表于国际顶尖学术期刊《免疫学》杂志上。

该研究组通过配对单细胞RNA测序和B细胞受体库测序来确定cHA疫苗接种诱导的B细胞的特异性、功能和亚群。该课题组研究人员已经证明，含有角鲨烯佐剂的cHA灭活疫苗诱导了针对茎结构域两个广泛中和的表位的robthemt活化B细胞和记忆B细胞（MBC）表型。急性质母细胞（PB）和MBC反应的总体特异性克隆重叠，表明B细胞趋同于这些广泛保护的表位。在免疫1年后，研究团队发现cHA疫苗重塑了HA特异性MBC池，以丰富茎结合B细胞。总之，这些数据表明，cHA疫苗诱导了针对HA茎结构域广泛保护性表位的持久和持久的B细胞反应，与血清学数据一致。

据介绍，在一项1期临床试验中，嵌合血凝素（cHA）免疫原诱导了针对保守血凝素（HA）茎结构域的抗体反应。

附：英文原文

Title: Long-lasting B cell convergence to distinct broadly reactive epitopes following vaccination with chimeric influenza virus hemagglutinins

Author: Jenna J. Guthmiller, Linda Yu-Ling Lan, Lei Li, Yanbin Fu, Sean A. Nelson, Carole Henry, Christopher T. Stamper, Henry A. Utset, Alec W. Freyn, Julianna Han, Olivia Stovicek, Jiaolong Wang, Nai-Ying Zheng, Min Huang, Haley L. Dugan, Micah E. Tepora, Xueyong Zhu, Yao-Qing Chen, Anna-Karin E. Palm, Dustin G. Shaw, Madhumathi Loganathan, Benjamin F. Francis, Jiayi Sun, Jordan Chervin, Chloe Troxell, Philip Meade, Nancy H.L. Leung, Sophie A. Valkenburg, Sarah Cobey, Benjamin J. Cowling, Ian A. Wilson, Adolfo García-Sastre, Raffael Nachbagauer, Andrew B. Ward, Lynda Coughlan, Florian Krammer, Patrick C. Wilson

Issue&Volume: 2025-03-24

Abstract: In a phase 1 clinical trial, a chimeric hemagglutinin (cHA) immunogen induced antibody responses against the conserved hemagglutinin (HA) stalk domain as designed. Here, we determined the specificity, function, and subsets of B cells induced by cHA vaccination by pairing single-cell RNA sequencing and B cell receptor repertoire sequencing. We have shown that the cHA-inactivated vaccine with a squalene-based adjuvant induced a robust activated B cell and memory B cell (MBC) phenotype against two broadly neutralizing epitopes in the stalk domain. The overall specificities of the acute plasmablast (PB) and MBC responses clonally overlapped, suggesting B cell convergence to these broadly protective epitopes. At 1 year post immunization, we identified that cHA vaccination reshaped the HA-specific MBC pool to enrich for stalk-binding B cells. Altogether, these data indicate the cHA vaccine induced robust and durable B cell responses against broadly protective epitopes of the HA stalk domain, in line with serological data.

DOI: 10.1016/j.immuni.2025.02.025

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00092-5