Analysis of mRNA vaccination-elicited RBD-specific memory B cells reveals strong but incomplete immune escape of the SARS-CoV-2 Omicron variant

• Published in: Immunity 2022-06, Vol.55 (6), p.1096-1104.e4
• Main Authors: Sokal, Aurélien, Broketa, Matteo, Barba-Spaeth, Giovanna, Meola, Annalisa, Fernández, Ignacio, Fourati, Slim, Azzaoui, Imane, de La Selle, Andrea, Vandenberghe, Alexis, Roeser, Anais, Bouvier-Alias, Magali, Crickx, Etienne, Languille, Laetitia, Michel, Marc, Godeau, Bertrand, Gallien, Sébastien, Melica, Giovanna, Nguyen, Yann, Zarrouk, Virginie, Canoui-Poitrine, Florence, Noizat-Pirenne, France, Megret, Jérôme, Pawlotsky, Jean-Michel, Fillatreau, Simon, Simon-Lorière, Etienne, Weill, Jean-Claude, Reynaud, Claude-Agnès, Rey, Félix A., Bruhns, Pierre, Chappert, Pascal, Mahévas, Matthieu
• Format: Article
• Language: English
• Subjects: affinity; Antibodies, Neutralizing; Antibodies, Viral; B cells; COVID-19; COVID-19 - prevention & control; Emerging diseases; germinal center; Human health and pathology; Humans; Immunology; Infectious diseases; Life Sciences; MBC; Memory B Cells; Microbiology and Parasitology; mRNA vaccine; Omicron; RNA, Messenger - genetics; SARS-CoV-2; Spike Glycoprotein, Coronavirus - genetics; Vaccination; Vaccinology; variants; Virology; VOC
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2022.04.002

The SARS-CoV-2 Omicron variant can escape neutralization by vaccine-elicited and convalescent antibodies. Memory B cells (MBCs) represent another layer of protection against SARS-CoV-2, as they persist after infection and vaccination and improve their affinity. Whether MBCs elicited by mRNA vaccines can recognize the Omicron variant remains unclear. We assessed the affinity and neutralization potency against the Omicron variant of several hundred naturally expressed MBC-derived monoclonal IgG antibodies from vaccinated COVID-19-recovered and -naive individuals. Compared with other variants of concern, Omicron evaded recognition by a larger proportion of MBC-derived antibodies, with only 30% retaining high affinity against the Omicron RBD, and the reduction in neutralization potency was even more pronounced. Nonetheless, neutralizing MBC clones could be found in all the analyzed individuals. Therefore, despite the strong immune escape potential of the Omicron variant, these results suggest that the MBC repertoire generated by mRNA vaccines still provides some protection against the Omicron variant in vaccinated individuals. [Display omitted] •Omicron evaded a large fraction of memory B cell (MBC)-derived antibodies•Only 30% of the MBCs retained high affinity against Omicron•Omicron neutralization by MBCs was reduced even more in all individuals•Neutralizing antibodies still represented more than 10% of the MBC repertoire Whether memory B cells (MBCs) elicited by SARS-CoV-2 mRNA vaccines can recognize the Omicron variant remains unclear. Sokal et al. show that compared with other variants of concern, Omicron evaded recognition and neutralization by a larger proportion of MBC-derived antibodies elicited after infection and/or vaccination. Nonetheless, Omicron-neutralizing MBC clones could be found in the repertoire of all the analyzed individuals.