학술논문
SARS-CoV-2 Omicron boosting induces de novo B cell response in humans
Document Type
Article
Author
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.
Source
Nature; 20230101, Issue: Preprints p1-7, 7p
Subject
Language
ISSN
00280836; 14764687
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.