Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Nature (London), 2021-08, Vol.596 (7870), p.109-113

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• SARS-CoV-2 mRNA-based vaccines are about 95% effective in preventing COVID-19 . 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 . 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.