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  • 标题:Epitope diversity of SARS-CoV-2 hyperimmune intravenous human immunoglobulins and neutralization of variants of concern
  • 本地全文:下载
  • 作者:Juanjie Tang ; Youri Lee ; Supriya Ravichandran
  • 期刊名称:iScience
  • 印刷版ISSN:2589-0042
  • 出版年度:2021
  • 卷号:24
  • 期号:9
  • 页码:1-15
  • DOI:10.1016/j.isci.2021.103006
  • 语种:English
  • 出版社:Elsevier
  • 摘要:SummaryHyperimmune 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.Graphical abstractDisplay OmittedHighlights•SARS-CoV-2 hCoV-2IG demonstrate highly diverse antibody epitope profile•SARS-CoV-2 hCoV-2IG lots neutralized SARS-CoV-2 variants better than CP•Significant reduction of hCoV-2IG binding to RBD-E484K compared with unmutated RBD•Higher hCoV-2IG dose would be required for SARS-CoV-2 variant infected patientsBiological sciences; Immunology; Immune response
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