Epitope diversity of SARS-CoV-2 hyperimmune intravenous human immunoglobulins and neutralization of variants of concern

Tang, Juanjie; Lee, Youri; Ravichandran, Supriya; Grubbs, Gabrielle; Huang, Chang; Stauft, Charles B.; Wang, Tony; Golding, Basil; Golding, Hana; Khurana, Surender

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 convalescent plasma (CP) against SARS-CoV-2 and emerging variants of concern (VOC). Epitope-mapping by Gene-Fragment-Phage display library (GFPDL) 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 (PsVNA) 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.