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Antigen presentation dynamics shape the antibody response to variants like SARS-CoV-2 Omicron after multiple vaccinations with the original strain
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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Author(s).
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9986127/ https://www.ncbi.nlm.nih.gov/pubmed/36952347 http://dx.doi.org/10.1016/j.celrep.2023.112256 |
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author | Yang, Leerang Van Beek, Matthew Wang, Zijun Muecksch, Frauke Canis, Marie Hatziioannou, Theodora Bieniasz, Paul D. Nussenzweig, Michel C. Chakraborty, Arup K. |
author_facet | Yang, Leerang Van Beek, Matthew Wang, Zijun Muecksch, Frauke Canis, Marie Hatziioannou, Theodora Bieniasz, Paul D. Nussenzweig, Michel C. Chakraborty, Arup K. |
author_sort | Yang, Leerang |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9986127 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The Author(s). |
record_format | MEDLINE/PubMed |
spelling | pubmed-99861272023-03-06 Antigen presentation dynamics shape the antibody response to variants like SARS-CoV-2 Omicron after multiple vaccinations with the original strain Yang, Leerang Van Beek, Matthew Wang, Zijun Muecksch, Frauke Canis, Marie Hatziioannou, Theodora Bieniasz, Paul D. Nussenzweig, Michel C. Chakraborty, Arup K. Cell Rep Article 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. The Author(s). 2023-04-25 2023-03-06 /pmc/articles/PMC9986127/ /pubmed/36952347 http://dx.doi.org/10.1016/j.celrep.2023.112256 Text en © 2023 The Author(s) Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article Yang, Leerang Van Beek, Matthew Wang, Zijun Muecksch, Frauke Canis, Marie Hatziioannou, Theodora Bieniasz, Paul D. Nussenzweig, Michel C. Chakraborty, Arup K. Antigen presentation dynamics shape the antibody response to variants like SARS-CoV-2 Omicron after multiple vaccinations with the original strain |
title | Antigen presentation dynamics shape the antibody response to variants like SARS-CoV-2 Omicron after multiple vaccinations with the original strain |
title_full | Antigen presentation dynamics shape the antibody response to variants like SARS-CoV-2 Omicron after multiple vaccinations with the original strain |
title_fullStr | Antigen presentation dynamics shape the antibody response to variants like SARS-CoV-2 Omicron after multiple vaccinations with the original strain |
title_full_unstemmed | Antigen presentation dynamics shape the antibody response to variants like SARS-CoV-2 Omicron after multiple vaccinations with the original strain |
title_short | Antigen presentation dynamics shape the antibody response to variants like SARS-CoV-2 Omicron after multiple vaccinations with the original strain |
title_sort | antigen presentation dynamics shape the antibody response to variants like sars-cov-2 omicron after multiple vaccinations with the original strain |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9986127/ https://www.ncbi.nlm.nih.gov/pubmed/36952347 http://dx.doi.org/10.1016/j.celrep.2023.112256 |
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