Omicron BA.1 breakthrough infection drives long-term remodeling of the memory B cell repertoire in vaccinated individuals
biorxiv(2023)
摘要
How infection by a viral variant showing antigenic drift impacts a preformed mature human memory B cell (MBC) repertoire remains an open question. Here, we studied the MBC response up to 6 months after Omicron BA.1 breakthrough infection in individuals previously vaccinated with three doses of mRNA vaccine. Longitudinal analysis, using single-cell multi-omics and functional analysis of monoclonal antibodies from RBD-specific MBCs, revealed that a BA.1 breakthrough infection mostly recruited pre-existing cross-reactive MBCs with limited de novo response against BA.1-restricted epitopes. Reorganization of clonal hierarchy and new rounds of germinal center reaction, however, combined to maintain diversity and induce progressive maturation of the MBC repertoire against common Hu-1 and BA.1, but not BA.5-restricted, SARS-CoV-2 Spike RBD epitopes. Such remodeling was further associated with marked improvement in overall neutralizing breadth and potency. These findings have fundamental implications for the design of future vaccination booster strategies.
### Competing Interest Statement
Outside of the submitted work, M. Mahevas. received research funds from GSK and personal fees from LFB and Amgen, J.-C.W. received consulting fees from Institut Merieux, P.B. received consulting fees from Regeneron Pharmaceuticals.
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关键词
infection,memory,cell,long-term
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