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

IF 25.5 1区 医学 Q1 IMMUNOLOGY
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, Patrick C. Wilson
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引用次数: 0

摘要

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。在这里,我们通过配对单细胞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。我们已经证明,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强大的活化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,我们发现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稳健和持久的B细胞应答,与血清学数据一致。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

Long-lasting B cell convergence to distinct broadly reactive epitopes following vaccination with chimeric influenza virus hemagglutinins
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.
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来源期刊
Immunity
Immunity 医学-免疫学
CiteScore
49.40
自引率
2.20%
发文量
205
审稿时长
6 months
期刊介绍: Immunity is a publication that focuses on publishing significant advancements in research related to immunology. We encourage the submission of studies that offer groundbreaking immunological discoveries, whether at the molecular, cellular, or whole organism level. Topics of interest encompass a wide range, such as cancer, infectious diseases, neuroimmunology, autoimmune diseases, allergies, mucosal immunity, metabolic diseases, and homeostasis.
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