TY - JOUR
T1 - SARS-CoV-2 Omicron boosting induces de novo B cell response in humans
AU - Alsoussi, Wafaa B.
AU - Malladi, Sameer Kumar
AU - Zhou, Julian Q.
AU - Liu, Zhuoming
AU - Ying, Baoling
AU - Kim, Wooseob
AU - Schmitz, Aaron J.
AU - Lei, Tingting
AU - Horvath, Stephen C.
AU - Sturtz, Alexandria J.
AU - McIntire, Katherine M.
AU - Evavold, Birk
AU - Han, Fangjie
AU - Scheaffer, Suzanne M.
AU - Fox, Isabella F.
AU - Mirza, Senaa F.
AU - Parra-Rodriguez, Luis
AU - Nachbagauer, Raffael
AU - Nestorova, Biliana
AU - Chalkias, Spyros
AU - Farnsworth, Christopher W.
AU - Klebert, Michael K.
AU - Pusic, Iskra
AU - Strnad, Benjamin S.
AU - Middleton, William D.
AU - Teefey, Sharlene A.
AU - Whelan, Sean P.J.
AU - Diamond, Michael S.
AU - Paris, Robert
AU - O’Halloran, Jane A.
AU - Presti, Rachel M.
AU - Turner, Jackson S.
AU - Ellebedy, Ali H.
N1 - Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2023/5/18
Y1 - 2023/5/18
N2 - 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 variants 1–4. SARS-CoV-2 booster immunizations in humans primarily recruit pre-existing memory B cells 5–9. 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.
AB - 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 variants 1–4. SARS-CoV-2 booster immunizations in humans primarily recruit pre-existing memory B cells 5–9. 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.
UR - http://www.scopus.com/inward/record.url?scp=85156269927&partnerID=8YFLogxK
U2 - 10.1038/s41586-023-06025-4
DO - 10.1038/s41586-023-06025-4
M3 - Article
C2 - 37011668
AN - SCOPUS:85156269927
SN - 0028-0836
VL - 617
SP - 592
EP - 598
JO - Nature
JF - Nature
IS - 7961
ER -