Potent neutralization by monoclonal human IgM against SARS-CoV-2 is impaired by class switch.

Callegari, Ilaria; Schneider, Mika; Berloffa, Giuliano; Mühlethaler, Tobias; Holdermann, Sebastian; Galli, Edoardo; Roloff, Tim; Boss, Renate; Infanti, Laura; Khanna, Nina; Egli, Adrian; Buser, Andreas; Zimmer, Gert; Derfuss, Tobias; Sanderson, Nicholas S R (2022). Potent neutralization by monoclonal human IgM against SARS-CoV-2 is impaired by class switch. EMBO reports, 23(7), e53956. EMBO press 10.15252/embr.202153956

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To investigate the class-dependent properties of anti-viral IgM antibodies, we use membrane antigen capture activated cell sorting to isolate spike-protein-specific B cells from donors recently infected with SARS-CoV-2, allowing production of recombinant antibodies. We isolate 20, spike-protein-specific antibodies of classes IgM, IgG, and IgA, none of which shows any antigen-independent binding to human cells. Two antibodies of class IgM mediate virus neutralization at picomolar concentrations, but this potency is lost following artificial switch to IgG. Although, as expected, the IgG versions of the antibodies appear to have lower avidity than their IgM parents, this is not sufficient to explain the loss of potency.

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