Epitope diversity of SARS-CoV-2 hyperimmune intravenous human immunoglobulins and neutralization of variants of concern
Juanjie Tang,
Youri Lee,
Supriya Ravichandran,
Gabrielle Grubbs,
Chang Huang,
Charles B. Stauft,
Tony Wang,
Basil Golding,
Hana Golding,
Surender Khurana
Affiliations
Juanjie Tang
Division of Viral Products, Office of Vaccines Research and Review, Silver Spring, MD 20993, USA
Youri Lee
Division of Viral Products, Office of Vaccines Research and Review, Silver Spring, MD 20993, USA
Supriya Ravichandran
Division of Viral Products, Office of Vaccines Research and Review, Silver Spring, MD 20993, USA
Gabrielle Grubbs
Division of Viral Products, Office of Vaccines Research and Review, Silver Spring, MD 20993, USA
Chang Huang
Division of Viral Products, Office of Vaccines Research and Review, Silver Spring, MD 20993, USA
Charles B. Stauft
Division of Viral Products, Office of Vaccines Research and Review, Silver Spring, MD 20993, USA
Tony Wang
Division of Viral Products, Office of Vaccines Research and Review, Silver Spring, MD 20993, USA
Basil Golding
Division of Plasma Protein Therapeutics, Office of Tissues and Therapeutic Proteins, Center for Biologics Evaluation and Research, Food and Drug Administrationa (FDA), 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA
Hana Golding
Division of Viral Products, Office of Vaccines Research and Review, Silver Spring, MD 20993, USA
Surender Khurana
Division of Viral Products, Office of Vaccines Research and Review, Silver Spring, MD 20993, USA; Corresponding author
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.
