Structural Adaptability of IgA and IgM Supports Broad SARS-CoV-2 Variant Neutralization.

ABSTRACT: Neutralizing emerging SARS-CoV-2 variants requires antibodies effective not only against epitope mutations but also under variable antigenic presentations. We assessed the neutralization capacity of the same anti-RBD monoclonal antibody (8A5) expressed as IgG, IgA, or IgM against 18 variants, identifying three neutralization classes: variants susceptible to all isotypes, variants resistant to IgG but sensitive to IgA/IgM, and variants resistant to all isotypes. Mutation analysis revealed that S371L-S373P-S375F disrupted IgG binding while partially preserving IgA/IgM activity, whereas L371F induced conformational changes abolishing all antibody interactions. Notably, some variants lacking these mutations still escaped IgG, suggesting geometric factors contribute to differential efficacy. To

SUBMITTER: Pisil Y 

PROVIDER: S-EPMC12805870 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature