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

ABSTRACT: In a phase I clinical trial, a chimeric hemagglutinin (cHA) immunogen induced antibody responses against the conserved 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 one-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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE260941 | GEO | 2025/03/04

REPOSITORIES: GEO

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

Project description:In a phase I clinical trial, a chimeric hemagglutinin (cHA) immunogen induced antibody responses against the conserved 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 one-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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B cell convergence to distinct broadly reactive epitopes following vaccination with chimeric influenza virus hemagglutinins

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