Omicron evaded a large fraction of memory B cell (MBC)-derived antibodies
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Only 30% of the MBCs retained high affinity against Omicron
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Omicron neutralization by MBCs was reduced even more in all individuals
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Neutralizing antibodies still represented more than 10% of the MBC repertoire
Summary
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.
Single-cell culture VDJ sequencing data were initially reported in Sokal et al., 2021b and all sequences used in this study are available as part of Table S1. All VDJ sequences were deposited as Targeted Locus Study projects at DDBJ/EMBL/GenBank under the accession numbers KFPV00000000-KFQZ00000000 (BioProject PRJNA819082, https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA819082). The version described in this paper is the first version, KFPV01000000-KFQZ01000000. Affinity and neutralization data are also included in Table S1, which has been deposited on Mendeley Data (https://data.mendeley.com/datasets/wwrxgn65h2/2).
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This paper does not report original code.
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Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.
