The vaccine platform used for COVID-19 primary immunization shapes the quality of the human B cell response to a vaccine boost

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.

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Publication Details

Journal
Science Translational Medicine
Published
2026-02-25
DOI
https://doi.org/10.1126/scitranslmed.aeb9837
Primary Topic
SARS-CoV-2 and COVID-19 Research
Type
article
Field-Weighted Citation Impact
0.00
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article

The vaccine platform used for COVID-19 primary immunization shapes the quality of the human B cell response to a vaccine boost

Anna P. Wald, Farida Laboune, Lauren McCormick, Christian Wake et al.
Science Translational Medicine
SARS-CoV-2 and COVID-19 Research
article

The vaccine platform used for COVID-19 primary immunization shapes the quality of the human B cell response to a vaccine boost

Anna P. Wald, Farida Laboune, Lauren McCormick, Christian Wake, Sarah Andrews, Coler Rhea, Diana Badillo, Marina Lee, Abby Spangler, Chaim A. Schramm, Noemia S. Lima, Rebecca C. Brady, Janet I. Archer, Jennifer Husson, Sonika Bhatnagar, Meagan E. Deming, Megan A Berman, Rahul Subramanian, Amy R. Henry, David Dobryzynski, HANA EL SAHLY, Jennifer Lee Dong, J.P. Martin, Daniel Szydlo, Jillian A. Zemanek, Samuel Li, Clara Domínguez Islas, Kumaravel Rajakumar, William L Catalano, Tara M. Babu, I-Ting Teng, Kirsten E. Lyke, Angie Price, Rahul Paul Choudhury, Seema U. Nayak, Richard Rupp, Martín Bäcker, Kristen W. Cohen, Christine M. Posavad, Christina A. Rostad, Kathleen M. Neuzil, Laura Porterfield, David A. Stephens, Robert W. Frenck, Daniel C. Douek, Robert L. Atmar, Peter D. Kwong, David Montefiori, Angela R. Branche, Amber Stanford, Christine M. Johnston, Mehul S. Suthar, 21-0012 Study Group, Stephen De Rosa, Adrian McDermott, Sonja Crandon, John Beigel, Susan Parker, Ann R. Falsey, Jennifer A. Whitaker, Nadine Rouphael, Lilin Lai, Michelle Dickey, M. Sasha E. Larsen, Paulina A. Rebolledo, Ian Shannon, John Hural, Evan J. Anderson, M. Juliana McElrath, Elizabeth R. Brown, Sarah O’Connell, Angelica C. Kottkamp, Yoav Pinto, Amanda Eaton, Bob Lin, Wendy A. Keitel
article en

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.

Science Translational MedicineVol. 18(838)
University of Maryland, Baltimore (US), Cincinnati Children's Hospital Medical Center (US), National Institutes of Health (US), Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa (ZA), Infectious Disease Research Institute (US), Kaiser Permanente Washington Health Research Institute (US), University of Pittsburgh (US), Baylor College of Medicine (US), University of Washington (US), University of Oxford (GB), NYU Langone Health (US), Fred Hutch Cancer Center (US), HOPE Clinic (US), Island Hospital (US), National Institute of Allergy and Infectious Diseases (US), Science Oxford (GB), Children's Healthcare of Atlanta (US), University of Rochester (US), The University of Texas Medical Branch at Galveston (US), New York University (US)
Openalex Percentile: Top 43%
SARS-CoV-2 and COVID-19 Research
DOISourceOpenAlex
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