Increased memory B cell potency and breadth after a SARS-CoV-2 mRNA boost
Open accessAbstract
The Omicron variant of SARS-CoV-2 infected many vaccinated and convalescent individuals 1–3 . Despite the reduced protection from infection, individuals who received three doses of an mRNA vaccine were highly protected from more serious consequences of infection 4 . Here we examine the memory B cell repertoire in a longitudinal cohort of individuals receiving three mRNA vaccine doses 5,6 . We find that the third dose is accompanied by an increase in, and evolution of, receptor-binding domain (RBD)-specific memory B cells. The increase is due to expansion of memory B cell clones that were present after the second dose as well as the emergence of new clones. The antibodies encoded by these cells showed significantly increased potency and breadth when compared with antibodies obtained after the second dose. Notably, the increase in potency was especially evident among newly developing clones of memory cells, which differed from persisting clones in targeting more conserved regions of the RBD. Overall, more than 50% of the analysed neutralizing antibodies in the memory compartment after the third mRNA vaccine dose neutralized the Omicron variant. Thus, individuals receiving three doses of an mRNA vaccine have a diverse memory B cell repertoire that can respond rapidly and produce antibodies capable of clearing even diversified variants such as Omicron. These data help to explain why a third dose of a vaccine that was not specifically designed to protect against variants is effective against variant-induced serious disease.
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A booster serves as a re-exposure to the virus, which creates new antibodies as well as additional and improved memory B-cell responses to fight off future infections.
“A booster serves as a re-exposure to the virus, which creates new antibodies as well as additional and improved memory B-cells responses to fight off future infections.”
From Effectiveness of COVID-19 vaccines against SARS-CoV-2 infection and severe outcomes in adults: a systematic review and meta-analysis of European studies published up to 22 January 2024 (2025) · cites this paper as [20]
The Discussion reports that a third mRNA vaccine dose boosts antibody responses and increases memory B cells with more potent, broader antibodies that can respond to later infection. It distinguishes exposure to vaccine antigen from exposure through infection, however, so the claim's description of the booster as re-exposure to the virus is not supported literally. (LLM, conf=0.83)
Experimental — accuracy not yet measuredBooster exposure improves the ability of memory B-cells to recognise unknown variants such as the Omicron strain.
“It has even been found that booster exposure also improves the ability of the memory B-cells to recognise unknown variants such as the Omicron strain [18, 20].”
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- Authors
- Muecksch, F., Wang, Z., Cho, A., Gaebler, C., Ben Tanfous, T., DaSilva, J., Bednarski, E., Ramos, V., Zong, S., Johnson, B., Raspe, R., Schaefer-Babajew, D., Shimeliovich, I., Daga, M., Yao, K.-H., Schmidt, F., Millard, K. G., Turroja, M., Jankovic, M., Oliveira, T. Y., Gazumyan, A., Caskey, M., Hatziioannou, T., Bieniasz, P. D., & Nussenzweig, M. C.
- Affiliations
- Rockefeller University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Bieniasz, Paul D.
- Nussenzweig, Michel C.
- ORCID
- Muecksch, Frauke
- Wang, Zijun
- Cho, Alice
- Gaebler, Christian
- DaSilva, Justin
- Bednarski, Eva
- Ramos, Victor
- Zong, Shuai
- Johnson, Brianna
- Raspe, Raphael
- Schaefer-Babajew, Dennis
- Shimeliovich, Irina
- Daga, Mridushi
- Yao, Kai-Hui
- Schmidt, Fabian
- Millard, Katrina G.
- Turroja, Martina
- Oliveira, Thiago Y.
- Gazumyan, Anna
- Caskey, Marina
- Hatziioannou, Theodora
- Bieniasz, Paul D.
- Nussenzweig, Michel C.
- Venue
- Nature
- Published
- 2022-04-21
- Volume
- 607
- Issue
- 7917
- Pages
- 128-134
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC9259484
- OpenAlex
- W4224232962
- Cited by
- 297
- References
- 45
- Citations by year
- 2026: 27 · 2025: 39 · 2024: 65 · 2023: 86 · 2022: 80
- FWCI
- 33.12
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- U.S. Department of Health & Human Services | National Institutes of Health (2U19AI111825, P01-AI138398-S1, UL1 TR001866, R01AI78788, R37-AI64003)
- Howard Hughes Medical Institute
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- SARS-CoV-2, Omicron variant, mRNA vaccines, booster vaccination, memory B cells, receptor binding domain, neutralizing antibodies, antibody potency, antibody breadth, B cell clones, longitudinal cohort
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Vaccines, mRNA Vaccines, Memory B Cells, Antibodies, Viral, Humans, Immunization, Secondary, RNA, Messenger, Antibodies, Neutralizing
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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