Guthmiller Jenna J, Yu-Ling Lan Linda, Li Lei, Fu Yanbin, Nelson Sean A, Henry Carole, Stamper Christopher T, Utset Henry A, Freyn Alec W, Han Julianna, Stovicek Olivia, Wang Jiaolong, Zheng Nai-Ying, Huang Min, Dugan Haley L, Tepora Micah E, Zhu Xueyong, Chen Yao-Qing, Palm Anna-Karin E, Shaw Dustin G, Loganathan Madhumathi, Francis Benjamin F, Sun Jiayi, Chervin Jordan, Troxell Chloe, Meade Philip, Leung Nancy H L, Valkenburg Sophie A, Cobey Sarah, Cowling Benjamin J, Wilson Ian A, García-Sastre Adolfo, Nachbagauer Raffael, Ward Andrew B, Coughlan Lynda, Krammer Florian, Wilson Patrick C
Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637, USA; Department on Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.
Immunity. 2025 Apr 8;58(4):980-996.e7. doi: 10.1016/j.immuni.2025.02.025. Epub 2025 Mar 24.
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.
在一项1期临床试验中，一种嵌合血凝素（cHA）免疫原按设计诱导了针对保守血凝素（HA）茎干结构域的抗体反应。在此，我们通过将单细胞RNA测序与B细胞受体库测序相结合，确定了cHA疫苗接种诱导的B细胞的特异性、功能和亚群。我们已经表明，含有基于角鲨烯佐剂的cHA灭活疫苗诱导了针对茎干结构域中两个广泛中和表位的强大活化B细胞和记忆B细胞（MBC）表型。急性浆母细胞（PB）和MBC反应的总体特异性在克隆水平上重叠，表明B细胞趋同于这些广泛保护性表位。免疫后1年，我们发现cHA疫苗接种重塑了HA特异性MBC库，以富集与茎干结合的B细胞。总之，这些数据表明cHA疫苗诱导了针对HA茎干结构域广泛保护性表位的强大而持久的B细胞反应，与血清学数据一致。
Sci Immunol. 2025-1-24
Vaccines (Basel). 2025-6-12
Brief Bioinform. 2024-5-23
Proc Natl Acad Sci U S A. 2023-10-31
Nat Rev Immunol. 2024-1
Proc Natl Acad Sci U S A. 2022-5-24
Cell Rep Methods. 2021-8-23
Zotero 插件