Language

English

Publication Date

2-25-2026

Journal

Science Translational Medicine

DOI

10.1126/scitranslmed.aeb9837

PMID

41739906

PMCID

PMC13492443

PubMedCentral® Posted Date

8-21-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

Improving long-term protective immunity elicited by prime-boost vaccinations requires a deeper understanding of the immunologic outcomes of different vaccine platforms. Given the variety of platforms used to develop vaccines against SARS-CoV-2, we reasoned that SARS-CoV-2 offered an opportunity to compare vaccine platforms in humans. We used flow cytometry and single-cell transcriptomics to explore the B cell response to different homologous and heterologous vaccine regimens. We found that an adenovirus vector prime followed by a messenger RNA (mRNA) vaccine boost showed the greatest short-term B cell expansion and preferentially elicited an activated atypical B cell subset that was associated with antibody binding titers against spike protein. In contrast, an mRNA primary series followed by homologous boost induced a different activated B cell subset with more proliferative potential and high frequencies of a long-lived resting memory subset. Moreover, immunoglobulin A (IgA)-expressing memory B cells had more somatic hypermutations than the predominant IgG-expressing B cell population. This heterogeneity in vaccine-elicited B cell responses underscores the potential of tailoring vaccine regimens that combine different platforms to achieve potent and durable protection against infectious diseases.

Keywords

Humans, COVID-19 Vaccines, SARS-CoV-2, COVID-19, B-Lymphocytes, Antibodies, Viral, Immunization, Secondary, Spike Glycoprotein, Coronavirus, Memory B Cells, Immunologic Memory, Immunoglobulin G

Published Open-Access

yes

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