SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses

Jackson S. Turner, Jane A. O’Halloran, Elizaveta Kalaidina, Wooseob Kim, Aaron J. Schmitz, Julian Q. Zhou, Tingting Lei, Mahima Thapa, Rita E. Chen, James Brett Case, Fatima Amanat, Adriana M. Rauseo, Alem Haile, Xuping Xie, Michael K. Klebert, Teresa Suessen, William D. Middleton, Pei Yong Shi, Florian Krammer, Sharlene A. TeefeyMichael S. Diamond, Rachel M. Presti, Ali H. Ellebedy

Research output: Contribution to journalArticlepeer-review

140 Scopus citations

Abstract

SARS-CoV-2 mRNA-based vaccines are about 95% effective in preventing COVID-191–5. The dynamics of antibody-secreting plasmablasts and germinal centre B cells induced by these vaccines in humans remain unclear. Here we examined antigen-specific B cell responses in peripheral blood (n = 41) and draining lymph nodes in 14 individuals who had received 2 doses of BNT162b2, an mRNA-based vaccine that encodes the full-length SARS-CoV-2 spike (S) gene1. Circulating IgG- and IgA-secreting plasmablasts that target the S protein peaked one week after the second immunization and then declined, becoming undetectable three weeks later. These plasmablast responses preceded maximal levels of serum anti-S binding and neutralizing antibodies to an early circulating SARS-CoV-2 strain as well as emerging variants, especially in individuals who had previously been infected with SARS-CoV-2 (who produced the most robust serological responses). By examining fine needle aspirates of draining axillary lymph nodes, we identified germinal centre B cells that bound S protein in all participants who were sampled after primary immunization. High frequencies of S-binding germinal centre B cells and plasmablasts were sustained in these draining lymph nodes for at least 12 weeks after the booster immunization. S-binding monoclonal antibodies derived from germinal centre B cells predominantly targeted the receptor-binding domain of the S protein, and fewer clones bound to the N-terminal domain or to epitopes shared with the S proteins of the human betacoronaviruses OC43 and HKU1. These latter cross-reactive B cell clones had higher levels of somatic hypermutation as compared to those that recognized only the SARS-CoV-2 S protein, which suggests a memory B cell origin. Our studies demonstrate that SARS-CoV-2 mRNA-based vaccination of humans induces a persistent germinal centre B cell response, which enables the generation of robust humoral immunity.

Original languageEnglish
Pages (from-to)109-113
Number of pages5
JournalNature
Volume596
Issue number7870
DOIs
StatePublished - Aug 5 2021

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