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Epitope diversity of SARS-CoV-2 hyperimmune intravenous human immunoglobulins and neutralization of variants of concern
oleh: Juanjie Tang, Youri Lee, Supriya Ravichandran, Gabrielle Grubbs, Chang Huang, Charles B. Stauft, Tony Wang, Basil Golding, Hana Golding, Surender Khurana
Format: | Article |
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Diterbitkan: | Elsevier 2021-09-01 |
Deskripsi
Summary: Hyperimmune immunoglobulin (hCoV-2IG) generated from SARS-CoV-2 convalescent plasma (CP) are under evaluation in clinical trials. Here we explored the antibody epitope repertoire, and virus neutralizing capacity of six hCoV-2IG batches as well as nine CP against SARS-CoV-2 and emerging variants of concern (VOCs). Epitope-mapping by gene-fragment phage display library spanning the SARS-CoV-2 spike demonstrated broad recognition of multiple antigenic sites spanning the entire spike that was higher for hCoV-2IG than CP, with predominant binding to the fusion peptide. In the pseudovirus neutralization assay and in the wild-type SARS-CoV-2 PRNT assay, hCoV-2IG lots showed higher titers against the WA-1 strain compared with CP. Neutralization of VOCs were reduced to different extent by hCoV-2IG lots but were higher than CP. Significant reduction of hCoV-2IG binding was observed to RBD-E484K followed by RBD-N501Y (but not RBD-K417N). This study suggests that post-exposure treatment with hCoV-2IG could be preferable to CP.