Drivers of differential antibody breadth in SARS-CoV-2 mRNA vaccination and infection 4823

Abstract Description mRNA vaccination for SARS-CoV-2 (CoV-2) results in initial polyclonal antibodies of greater breadth compared to those stimulated by viral infection. Cellular, immunogenetic and antigenic factors leading to human antibody responses with broad viral variant recognition are poorly defined. Existing databases of CoV-2 binding antibodies have limited data about patient and B cell subset origins of the antibodies and their antigen variant binding. We used highly multiplexed panels of DNA-tagged CoV-2 antigens including Spike receptor binding domains from up to 20 viral variants to label and sort 6,262 antigen-binding B cells from peripheral blood of mRNA vaccinees, infected patients and the spleen and lymph nodes of deceased organ donors. Single-cell transcriptome and antigen DNA-tag data showed antigen-specific B cells enriched in a circulating class-switched memory subset with evidence of recent germinal center exposure, and in CD11c+ atypical B cells. Surprisingly, mRNA vaccination preferentially stimulates a subset of B cell receptor (BCR)-defined clonotypes, resulting in greater initial antigen binding breadth. Spleens show greater variant binding breadth than blood B cells from the initial months post-vaccination or infection. Together, these results systematically define the influence of CoV-2 mRNA vaccination and infection on particular B cell receptors and clonotypes, a topic of increasing importance as mRNA vaccination is evaluated for other pathogens. Funding Sources Supported by NIH/NIAID R01AI127877, NIH/NIAID R01AI130398, NIH 1U54CA260517, David Crown Foundation endowment/COVID-19 gift funds, NIH HIPC U19AI090023, U19AI057266, Sean N Parker Foundation/Sunshine Foundation, Early Postdoc.Mobility Fellowship Stipend (SNSF), Fulbright Fellowship, NHMRC Investigator grant, NSFC32270937/NSFC82341068 (Chinese NSF), Coulter COVID-19 Rapid Response Award, MSD kits. Topic Categories Viral Immunology (VIR)

Authors

Institutions

Publication Details

Journal
The Journal of Immunology
Published
2025-11-01
DOI
https://doi.org/10.1093/jimmun/vkaf283.2440
Primary Topic
SARS-CoV-2 and COVID-19 Research
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Drivers of differential antibody breadth in SARS-CoV-2 mRNA vaccination and infection 4823

Brandon Lam, Ji-Yeun Lee, Prasanti Kotagiri, Jacob N. Wohlstadter et al.
The Journal of Immunology
SARS-CoV-2 and COVID-19 Research
article

Drivers of differential antibody breadth in SARS-CoV-2 mRNA vaccination and infection 4823

Brandon Lam, Ji-Yeun Lee, Prasanti Kotagiri, Jacob N. Wohlstadter, Brian Ha, Emily Haraguchi, Mark M. Davis, Jackson Schuetz, Donna Smith, Linda M. Liao, Fan Yang, Bali Pulendran, Katharina Röltgen, Prabhu S. Arunachalam, Erin Craig, Ramona A. Hoh, Stuart A. Scott, Carsten Utoft Niemann, Taylor Pursell, Chandler Ho, Benjamin A. Pinsky, Scott D. Boyd, Jumana Afaghani, Monali Manohar, Sean Van Slyck, George B. Sigal, Oliver F. Wirz, Iris Chang, Jeremy Minshull, Sandra C. A. Nielsen, Andrea Fernandes, Emmanuelle Do, Molly Hunter, Kari Christine Nadeau
article en

Abstract

Abstract Description mRNA vaccination for SARS-CoV-2 (CoV-2) results in initial polyclonal antibodies of greater breadth compared to those stimulated by viral infection. Cellular, immunogenetic and antigenic factors leading to human antibody responses with broad viral variant recognition are poorly defined. Existing databases of CoV-2 binding antibodies have limited data about patient and B cell subset origins of the antibodies and their antigen variant binding. We used highly multiplexed panels of DNA-tagged CoV-2 antigens including Spike receptor binding domains from up to 20 viral variants to label and sort 6,262 antigen-binding B cells from peripheral blood of mRNA vaccinees, infected patients and the spleen and lymph nodes of deceased organ donors. Single-cell transcriptome and antigen DNA-tag data showed antigen-specific B cells enriched in a circulating class-switched memory subset with evidence of recent germinal center exposure, and in CD11c+ atypical B cells. Surprisingly, mRNA vaccination preferentially stimulates a subset of B cell receptor (BCR)-defined clonotypes, resulting in greater initial antigen binding breadth. Spleens show greater variant binding breadth than blood B cells from the initial months post-vaccination or infection. Together, these results systematically define the influence of CoV-2 mRNA vaccination and infection on particular B cell receptors and clonotypes, a topic of increasing importance as mRNA vaccination is evaluated for other pathogens. Funding Sources Supported by NIH/NIAID R01AI127877, NIH/NIAID R01AI130398, NIH 1U54CA260517, David Crown Foundation endowment/COVID-19 gift funds, NIH HIPC U19AI090023, U19AI057266, Sean N Parker Foundation/Sunshine Foundation, Early Postdoc.Mobility Fellowship Stipend (SNSF), Fulbright Fellowship, NHMRC Investigator grant, NSFC32270937/NSFC82341068 (Chinese NSF), Coulter COVID-19 Rapid Response Award, MSD kits. Topic Categories Viral Immunology (VIR)

The Journal of ImmunologyVol. 214(Supplement_1)
Swiss Tropical and Public Health Institute (CH), University of California, San Francisco (US), Beth Israel Deaconess Hospital (US), Stanford Health Care (US), ATUM (United States) (US), Stanford Medicine (US), Shenzhen Institutes of Advanced Technology (CN), Sierra Engineering (United States) (US), Meso Scale Discovery (United States) (US), Monash University (AU), Stanford University (US)
Openalex Percentile: Top 58%
SARS-CoV-2 and COVID-19 Research
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.