Immune imprinting, breadth of variant recognition, and germinal center response in human SARS-CoV-2 infection and vaccination

Katharina Röltgen(Stanford University), Sandra C. A. Nielsen(Stanford University), Oscar Silva(Stanford University), Sheren Younes(Stanford University), Maxim Zaslavsky(Stanford University), Cristina Costales(Stanford University), Fan Yang(Stanford University), Oliver F. Wirz(Stanford University), Daniel Solis(Stanford University), Ramona A. Hoh(Stanford University), Aihui Wang(Stanford University), Prabhu S. Arunachalam(Stanford University), Deana R.C. Colburg(Stanford University), Shuchun Zhao(Stanford University), Emily Haraguchi(Stanford University), Alexandra S. Lee(Stanford University), Mihir Shah(Stanford University), Monali Manohar(Stanford University), Iris Chang(Stanford University), Fei Gao(Stanford University), Vamsee Mallajosyula(Stanford University), Chunfeng Li(Stanford University), James Liu(Stanford Health Care), Massa J. Shoura(Stanford University), Sayantani Sindher(Stanford University), Ella Parsons(Stanford University), Naranjargal Dashdorj(Mongolian University of Life Sciences), Naranbaatar Dashdorj(Mongolian University of Life Sciences), R. J. Monroe(Advanced Cell Diagnostics (United States)), Geidy E. Serrano(Banner Sun Health Research Institute), Thomas G. Beach(Banner Sun Health Research Institute), R. Sharon Chinthrajah(Stanford University), Gregory W. Charville(Stanford University), James L. Wilbur(Meso Scale Discovery (United States)), Jacob N. Wohlstadter(Meso Scale Discovery (United States)), Mark M. Davis(Howard Hughes Medical Institute), Bali Pulendran(Stanford University), Megan L. Troxell(Stanford University), George B. Sigal(Meso Scale Discovery (United States)), Yasodha Natkunam(Stanford University), Benjamin A. Pinsky(Stanford Medicine), Kari C. Nadeau(Stanford University), Scott D. Boyd(Stanford Medicine)
Cell
January 25, 2022
10.1016/j.cell.2022.01.018
Cited by 493Open Access
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Abstract

During the SARS-CoV-2 pandemic, novel and traditional vaccine strategies have been deployed globally. We investigated whether antibodies stimulated by mRNA vaccination (BNT162b2), including third-dose boosting, differ from those generated by infection or adenoviral (ChAdOx1-S and Gam-COVID-Vac) or inactivated viral (BBIBP-CorV) vaccines. We analyzed human lymph nodes after infection or mRNA vaccination for correlates of serological differences. Antibody breadth against viral variants is lower after infection compared with all vaccines evaluated but improves over several months. Viral variant infection elicits variant-specific antibodies, but prior mRNA vaccination imprints serological responses toward Wuhan-Hu-1 rather than variant antigens. In contrast to disrupted germinal centers (GCs) in lymph nodes during infection, mRNA vaccination stimulates robust GCs containing vaccine mRNA and spike antigen up to 8 weeks postvaccination in some cases. SARS-CoV-2 antibody specificity, breadth, and maturation are affected by imprinting from exposure history and distinct histological and antigenic contexts in infection compared with vaccination.

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