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

JS Turner, JA O'Halloran, E Kalaidina, W Kim… - Nature, 2021 - nature.com
JS Turner, JA O'Halloran, E Kalaidina, W Kim, AJ Schmitz, JQ Zhou, T Lei, M Thapa
Nature, 2021nature.com
Abstract SARS-CoV-2 mRNA-based vaccines are about 95% effective in preventing COVID-
19 1, 2, 3, 4, 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) gene 1. Circulating IgG-and IgA-secreting …
Abstract
SARS-CoV-2 mRNA-based vaccines are about 95% effective in preventing COVID-19 1, 2, 3, 4, 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) gene 1. 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.
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