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• W3115803024 abstract "SUMMARY Although humoral immunity is essential for control of SARS-CoV-2, the molecular composition, binding epitopes and effector functions of the immunoglobulin G (IgG) antibodies that circulate in blood plasma following infection are unknown. Proteomic deconvolution of the circulating IgG repertoire (Ig-Seq 1 ) to the spike ectodomain (S-ECD 2 ) in four convalescent study subjects revealed that the plasma response is oligoclonal and directed predominantly (>80%) to S-ECD epitopes that lie outside the receptor binding domain (RBD). When comparing antibodies directed to either the RBD, the N-terminal domain (NTD) or the S2 subunit (S2) in one subject, just four IgG lineages (1 anti-S2, 2 anti-NTD and 1 anti-RBD) accounted for 93.5% of the repertoire. Although the anti-RBD and one of the anti-NTD antibodies were equally potently neutralizing in vitro , we nonetheless found that the anti-NTD antibody was sufficient for protection to lethal viral challenge, either alone or in combination as a cocktail where it dominated the effect of the other plasma antibodies. We identified in vivo protective plasma anti-NTD antibodies in 3/4 subjects analyzed and discovered a shared class of antibodies targeting the NTD that utilize unmutated or near-germline IGHV1-24, the most electronegative IGHV gene in the human genome. Structural analysis revealed that binding to NTD is dominated by interactions with the heavy chain, accounting for 89% of the entire interfacial area, with germline residues uniquely encoded by IGHV1-24 contributing 20% (149 Å 2 ). Together with recent reports of germline IGHV1-24 antibodies isolated by B-cell cloning 3,4 our data reveal a class of shared IgG antibodies that are readily observed in convalescent plasma and underscore the role of NTD-directed antibodies in protection against SARS-CoV-2 infection." @default.
• W3115803024 created "2021-01-05" @default.
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• W3115803024 date "2020-12-21" @default.
• W3115803024 modified "2023-10-09" @default.
• W3115803024 title "Prevalent, protective, and convergent IgG recognition of SARS-CoV-2 non-RBD spike epitopes in COVID-19 convalescent plasma" @default.
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• W3115803024 doi "https://doi.org/10.1101/2020.12.20.423708" @default.
• W3115803024 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7781304" @default.
• W3115803024 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33398269" @default.
• W3115803024 hasPublicationYear "2020" @default.
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