SARS-CoV-2 Omicron boosting induces de novo B cell response in humans.

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 variants1-4. SARS-CoV-2 booster immunizations in humans primarily recruit pre-existing memory B cells5-9. 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.

Alsoussi WB ，Malladi SK ，Zhou JQ ，Liu Z ，Ying B ，Kim W ，Schmitz AJ ，Lei T ，Horvath SC ，Sturtz AJ ，McIntire KM ，Evavold B ，Han F ，Scheaffer SM ，Fox IF ，Mirza SF ，Parra-Rodriguez L ，Nachbagauer R ，Nestorova B ，Chalkias S ，Farnsworth CW ，Klebert MK ，Pusic I ，Strnad BS ，Middleton WD ，Teefey SA ，Whelan SPJ ，Diamond MS ，Paris R ，O'Halloran JA ，Presti RM ，Turner JS ，Ellebedy AH ... -  《-》

SARS-CoV-2 Omicron boosting induces de novo B cell response in humans.

Alsoussi WB ，Malladi SK ，Zhou JQ ，Liu Z ，Ying B ，Kim W ，Schmitz AJ ，Lei T ，Horvath SC ，Sturtz AJ ，McIntire KM ，Evavold B ，Han F ，Scheaffer SM ，Fox IF ，Parra-Rodriguez L ，Nachbagauer R ，Nestorova B ，Chalkias S ，Farnsworth CW ，Klebert MK ，Pusic I ，Strnad BS ，Middleton WD ，Teefey SA ，Whelan SPJ ，Diamond MS ，Paris R ，O'Halloran JA ，Presti RM ，Turner JS ，Ellebedy AH ... -  《-》

Ipsilateral or contralateral boosting of mice with mRNA vaccines confers equivalent immunity and protection against a SARS-CoV-2 Omicron strain.

Ying B ，Liang C-Y ，Desai P ，Scheaffer SM ，Elbashir SM ，Edwards DK ，Thackray LB ，Diamond MS ... -  《-》

Fourth dose bivalent COVID-19 vaccines outperform monovalent boosters in eliciting cross-reactive memory B cells to Omicron subvariants.

Fryer HA ，Geers D ，Gommers L ，Zaeck LM ，Tan NH ，Jones-Freeman B ，Goorhuis A ，Postma DF ，Visser LG ，Hogarth PM ，Koopmans MPG ，GeurtsvanKessel CH ，O'Hehir RE ，van der Kuy PHM ，de Vries RD ，van Zelm MC ... -  《-》

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

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.

Turner JS ，O'Halloran JA ，Kalaidina E ，Kim W ，Schmitz AJ ，Zhou JQ ，Lei T ，Thapa M ，Chen RE ，Case JB ，Amanat F ，Rauseo AM ，Haile A ，Xie X ，Klebert MK ，Suessen T ，Middleton WD ，Shi PY ，Krammer F ，Teefey SA ，Diamond MS ，Presti RM ，Ellebedy AH ... -  《-》