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

Autor: Jenna Guthmiller, Linda Yu-Ling Lan, Lei Li, Carole Henry, Christopher Stamper, Henry Utset, Alec Freyn, Julianna Han, Olivia Stovicek, Jiaolong Wang, Nai-Ying Zheng, Min Huang, Haley Dugan, Micah Tepora, Xueyong Zhu, Yao-Qing Chen, Anna-Karin Palm, Dustin Shaw, Madhumanthi Loganathan, Benjamin Francis, Mia McNair, Philip Mead, Ian Wilson, Adolfo Garcia-Sastre, Raffael Nachbagauer, Peter Palese, Andrew Ward, Lynda Coughlan, Florian Krammer, Patrick Wilson
Rok vydání: 2023
Popis: In a phase I clinical trial, the chimeric hemagglutinin (cHA) immunogen induced antibody responses against the conserved HA stalk domain. However, the landscape of the B cell specificities and subsets induced by this vaccine remain undetermined. Here, we paired single cell RNA-sequencing and B cell receptor repertoire sequencing to analyze the relationship between transcriptome and B cell specificity following cHA immunization. We show that the cHA inactivated vaccine with a squalene-based adjuvant induced a robust activated B cell and memory B cell phenotype against two broadly neutralizing epitopes of the stalk domain. The overall specificities of the acute plasmablast and memory B cell responses were distinct, with the plasmablast compartment largely targeting non-neutralizing epitopes of the HA stalk. Altogether, these data indicate the B cell landscape following cHA vaccination includes diverse B cell subsets that are differentially induced by distinct vaccine formulations, including memory and de novo B cell responses against diverse broadly conserved epitopes.
Databáze: OpenAIRE