SARS-CoV-2 Omicron boosting induces de novo B cell response in humans

Alsoussi, Wafaa B.; Malladi, Sameer Kumar; Zhou, Julian Q.; Liu, Zhuoming; Ying, Baoling; Kim, Wooseob; Schmitz, Aaron J.; Lei, Tingting; Horvath, Stephen C.; Sturtz, Alexandria J.; McIntire, Katherine M.; Evavold, Birk; Han, Fangjie; Scheaffer, Suzanne M.; Fox, Isabella F.; Mirza, Senaa F.; Parra-Rodriguez, Luis; Nachbagauer, Raffael; Nestorova, Biliana; Chalkias, Spyros; Farnsworth, Christopher W.; Klebert, Michael K.; Pusic, Iskra; Strnad, Benjamin S.; Middleton, William D.; Teefey, Sharlene A.; Whelan, Sean P. J.; Diamond, Michael S.; Paris, Robert; O’Halloran, Jane A.; Presti, Rachel M.; Turner, Jackson S.; Ellebedy, Ali H.

SARS-CoV-2 Omicron boosting induces de novo B cell response in humans

Wafaa B. Alsoussi, Sameer Kumar Malladi, Julian Q. Zhou, Zhuoming Liu, Baoling Ying, Wooseob Kim, Aaron J. Schmitz, Tingting Lei, Stephen C. Horvath, Alexandria J. Sturtz, Katherine M. McIntire, Birk Evavold, Fangjie Han, Suzanne M. Scheaffer, Isabella F. Fox, Senaa F. Mirza, Luis Parra-Rodriguez, Raffael Nachbagauer, Biliana Nestorova, Spyros Chalkias, Christopher W. Farnsworth, Michael K. Klebert, Iskra Pusic, Benjamin S. Strnad, William D. Middleton, Sharlene A. Teefey, Sean P. J. Whelan, Michael S. Diamond, Robert Paris, Jane A. O’Halloran, Rachel M. Presti, Jackson S. Turner () and Ali H. Ellebedy ()
Additional contact information
Wafaa B. Alsoussi: Washington University School of Medicine
Sameer Kumar Malladi: Washington University School of Medicine
Julian Q. Zhou: Washington University School of Medicine
Zhuoming Liu: Washington University School of Medicine
Baoling Ying: Washington University School of Medicine
Wooseob Kim: Washington University School of Medicine
Aaron J. Schmitz: Washington University School of Medicine
Tingting Lei: Washington University School of Medicine
Stephen C. Horvath: Washington University School of Medicine
Alexandria J. Sturtz: Washington University School of Medicine
Katherine M. McIntire: Washington University School of Medicine
Birk Evavold: Washington University School of Medicine
Fangjie Han: Washington University School of Medicine
Suzanne M. Scheaffer: Washington University School of Medicine
Isabella F. Fox: Washington University School of Medicine
Senaa F. Mirza: Washington University School of Medicine
Luis Parra-Rodriguez: Washington University School of Medicine
Raffael Nachbagauer: Moderna
Biliana Nestorova: Moderna
Spyros Chalkias: Moderna
Christopher W. Farnsworth: Washington University School of Medicine
Michael K. Klebert: Washington University School of Medicine
Iskra Pusic: Washington University School of Medicine
Benjamin S. Strnad: Washington University School of Medicine
William D. Middleton: Washington University School of Medicine
Sharlene A. Teefey: Washington University School of Medicine
Sean P. J. Whelan: Washington University School of Medicine
Michael S. Diamond: Washington University School of Medicine
Robert Paris: Moderna
Jane A. O’Halloran: Washington University School of Medicine
Rachel M. Presti: Washington University School of Medicine
Jackson S. Turner: Washington University School of Medicine
Ali H. Ellebedy: Washington University School of Medicine

Nature, 2023, vol. 617, issue 7961, 592-598

Abstract: Abstract The primary two-dose SARS-CoV-2 mRNA vaccine series are strongly immunogenic in humans, but the emergence of highly infectious variants necessitated additional doses and the development of vaccines aimed at the new variants1–4. SARS-CoV-2 booster immunizations in humans primarily recruit pre-existing memory B cells5–9. However, it remains unclear whether the additional doses induce germinal centre reactions whereby re-engaged B cells can further mature, and whether variant-derived vaccines can elicit responses to variant-specific epitopes. Here we show that boosting with an mRNA vaccine against the original monovalent SARS-CoV-2 mRNA vaccine or the bivalent B.1.351 and B.1.617.2 (Beta/Delta) mRNA vaccine induced robust spike-specific germinal centre B cell responses in humans. The germinal centre response persisted for at least eight weeks, leading to significantly more mutated antigen-specific bone marrow plasma cell and memory B cell compartments. Spike-binding monoclonal antibodies derived from memory B cells isolated from individuals boosted with either the original SARS-CoV-2 spike protein, bivalent Beta/Delta vaccine or a monovalent Omicron BA.1-based vaccine predominantly recognized the original SARS-CoV-2 spike protein. Nonetheless, using a more targeted sorting approach, we isolated monoclonal antibodies that recognized the BA.1 spike protein but not the original SARS-CoV-2 spike protein from individuals who received the mRNA-1273.529 booster; these antibodies were less mutated and recognized novel epitopes within the spike protein, suggesting that they originated from naive B cells. Thus, SARS-CoV-2 booster immunizations in humans induce robust germinal centre B cell responses and can generate de novo B cell responses targeting variant-specific epitopes.

Date: 2023
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DOI: 10.1038/s41586-023-06025-4

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