Antigen presentation dynamics shape the antibody response to variants like SARS-CoV-2 Omicron after multiple vaccinations with the original strain
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1-s2.0-S221112472300267X-main.pdf
Description
Published version
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5.43 MB
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Checksum (MD5)
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Author(s)
Yang, Leerang
Van Beek, Matthew
Wang, Zijun
Muecksch, Frauke
Canis, Marie
Hatziioannou, Theodora
Bieniasz, Paul D
Nussenzweig, Michel C
Chakraborty, Arup K
Date Issued
April 2023
Journal
Cell Reports
Publisher
Elsevier BV
Citation
Yang, Leerang, Van Beek, Matthew, Wang, Zijun, Muecksch, Frauke, Canis, Marie et al. 2023. "Antigen presentation dynamics shape the antibody response to variants like SARS-CoV-2 Omicron after multiple vaccinations with the original strain." Cell Reports, 42 (4).
Version
Final published version
Abstract
The Omicron variant of SARS-CoV-2 is not effectively neutralized by most antibodies elicited by two doses of mRNA vaccines, but a third dose increases anti-Omicron neutralizing antibodies. We reveal mechanisms underlying this observation by combining computational modeling with data from vaccinated humans. After the first dose, limited antigen availability in germinal centers (GCs) results in a response dominated by B cells that target immunodominant epitopes that are mutated in an Omicron-like variant. After the second dose, these memory cells expand and differentiate into plasma cells that secrete antibodies that are thus ineffective for such variants. However, these pre-existing antigen-specific antibodies transport antigen efficiently to secondary GCs. They also partially mask immunodominant epitopes. Enhanced antigen availability and epitope masking in secondary GCs together result in generation of memory B cells that target subdominant epitopes that are less mutated in Omicron. The third dose expands these cells and boosts anti-variant neutralizing antibodies.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Physics
Massachusetts Institute of Technology. Department of Chemistry
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Ragon Institute of MGH, MIT and Harvard
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Creative Commons Attribution-NonCommercial-NoDerivs
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DOI of Published Version
https://doi.org/10.1016/j.celrep.2023.112256
