Anti- SARS-CoV-2 Receptor Binding Domain Antibody Evolution after mRNA Vaccination
Open accessPreprint — published as 10.1038/s41586-021-04060-7
Abstract
Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces B-cell responses that continue to evolve for at least one year. During that time, memory B cells express increasingly broad and potent antibodies that are resistant to mutations found in variants of concern 1 . As a result, vaccination of coronavirus disease 2019 (COVID-19) convalescent individuals with currently available mRNA vaccines produces high levels of plasma neutralizing activity against all variants tested 1, 2 . Here, we examine memory B cell evolution 5 months after vaccination with either Moderna (mRNA-1273) or Pfizer- BioNTech (BNT162b2) mRNA vaccines in a cohort of SARS-CoV-2 naïve individuals. Between prime and boost, memory B cells produce antibodies that evolve increased neutralizing activity, but there is no further increase in potency or breadth thereafter. Instead, memory B cells that emerge 5 months after vaccination of naïve individuals express antibodies that are similar to those that dominate the initial response. While individual memory antibodies selected over time by natural infection have greater potency and breadth than antibodies elicited by vaccination, the overall neutralizing potency of plasma is greater following vaccination. These results suggest that boosting vaccinated individuals with currently available mRNA vaccines will increase plasma neutralizing activity but may not produce antibodies with breadth equivalent to those obtained by vaccinating convalescent individuals.
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mRNA vaccines induce robust germinal center responses in humans, resulting in memory B cells specific for full-length spike and RBD.
“mRNA vaccines induce robust germinal center responses in humans (14, 15), which result in memory B cells that are specific for both the full-length SARS-CoV-2 spike protein and the spike receptor-binding domain (RBD) (16–18).”
From mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern (2021) · cites this paper as [17]
Variant binding developed rapidly after two-dose mRNA vaccination but evolved more slowly after infection.
“Variant binding developed rapidly after two-dose mRNA vaccination but evolved more slowly after infection, consistent with conclusions drawn from other approaches (17).”
From mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern (2021) · cites this paper as [17]
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References 65 · Cited by 275
- Authors
- Cho, A., Muecksch, F., Schaefer-Babajew, D., Wang, Z., Finkin, S., Gaebler, C., Ramos, V., Cipolla, M., Mendoza, P., Agudelo, M., Bednarski, E., DaSilva, J., Shimeliovich, I., Dizon, J., Daga, M., Millard, K., Turroja, M., Schmidt, F., Zhang, F., Tanfous, T. B., Jankovic, M., Oliveria, T. Y., Gazumyan, A., Caskey, M., Bieniasz, P. D., Hatziioannou, T., & Nussenzweig, M. C.
- Affiliations
- Rockefeller University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Caskey, Marina
- Bieniasz, Paul D.
- Nussenzweig, Michel C.
- ORCID
- Cho, Alice
- Muecksch, Frauke
- Schaefer-Babajew, Dennis
- Wang, Zijun
- Finkin, Shlomo
- Gaebler, Christian
- Cipolla, Melissa
- Mendoza, Pilar
- Agudelo, Marianna
- Bednarski, Eva
- DaSilva, Justin
- Shimeliovich, Irina
- Dizon, Juan
- Daga, Mridushi
- Millard, Katrina
- Turroja, Martina
- Schmidt, Fabian
- Zhang, Fengwen
- Tanfous, Tarek Ben
- Gazumyan, Anna
- Caskey, Marina
- Bieniasz, Paul D.
- Nussenzweig, Michel C.
- Venue
- Nature
- Publisher
- openRxiv
- Published
- 2021-07-29
- Volume
- 600
- Issue
- 7889
- Pages
- 517-522
- ISSN
- 0028-0836 (ISSN-L)
- PMC
- PMC8674133
- OpenAlex
- W3201962062
- Cited by
- 275
- References
- 65
- Citations by year
- 2026: 10 · 2025: 18 · 2024: 30 · 2023: 51 · 2022: 134 · 2021: 31 · 2013: 1
- FWCI
- 19.62
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Nature (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (P01-AI138398-S1, COVID-19, AI111825, TR001866, UL1TR001866)
- National Institute of Allergy and Infectious Diseases (R01AI078788, U19AI111825, R37AI064003)
- National Center for Advancing Translational Sciences (TR001866)
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- SARS-CoV-2, COVID-19 vaccination, mRNA vaccines, BNT162b2, mRNA-1273, memory B cells, antibody evolution, receptor binding domain, neutralizing antibodies, antibody breadth, antibody potency, booster vaccination, SARS-CoV-2 variants of concern, convalescent patients
- MeSH terms
- Protein Domains, COVID-19 Vaccines, mRNA Vaccines, BNT162 Vaccine, 2019-nCoV Vaccine mRNA-1273, Memory B Cells, Adult, Aged, Antibodies, Monoclonal, Antibodies, Viral, Antibody Affinity, Cross Reactions, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Middle Aged, Neutralization Tests, Vaccines, Synthetic, Cohort Studies, Epitopes, B-Lymphocyte, Evolution, Molecular, Young Adult, Antibodies, Neutralizing, Spike Glycoprotein, Coronavirus
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