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Publication Abstract from PubMed

Somatic hypermutation (SHM) drives affinity maturation and continues over months in SARS-CoV-2-neutralizing antibodies (nAbs). However, several potent SARS-CoV-2 antibodies carry no or only a few mutations, leaving the question of how ongoing SHM affects neutralization unclear. Here, we reverted variable region mutations of 92 antibodies and tested their impact on SARS-CoV-2 binding and neutralization. Reverting higher numbers of mutations correlated with decreasing antibody functionality. However, for some antibodies, including antibodies of the public clonotype VH1-58, neutralization of Wu01 remained unaffected. Although mutations were dispensable for Wu01-induced VH1-58 antibodies to neutralize Alpha, Beta, and Delta variants, they were critical for Omicron BA.1/BA.2 neutralization. We exploited this knowledge to convert the clinical antibody tixagevimab into a BA.1/BA.2 neutralizer. These findings broaden our understanding of SHM as a mechanism that not only improves antibody responses during affinity maturation but also contributes to antibody diversification, thus increasing the chances of neutralizing viral escape variants.

Somatic hypermutation introduces bystander mutations that prepare SARS-CoV-2 antibodies for emerging variants.,Korenkov M, Zehner M, Cohen-Dvashi H, Borenstein-Katz A, Kottege L, Janicki H, Vanshylla K, Weber T, Gruell H, Koch M, Diskin R, Kreer C, Klein F Immunity. 2023 Dec 12;56(12):2803-2815.e6. doi: 10.1016/j.immuni.2023.11.004. , Epub 2023 Nov 29. PMID:38035879^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.