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

Abstract

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.

Immunodominant Linear B-Cell Epitopes of SARS-CoV-2 Spike, Identified by Sera from K18-hACE2 Mice Infected with the WT or Variant Viruses

“…Indeed, we bring evidence that the various sera cross-neutralize the WT and VOCs under study (Figure 3). Our results are in line with those reported by Tang J. et al 2021 following a study addressing the neutralization potential of several hyper-immunoglobulin and convalescent plasma preparations generated against WT SARS-CoV-2 towards the B.1.1.7 and B.1.351 VOCs [43]. Furthermore, the individual ability of monoclonal antibodies generated against the WT spike glycoprotein to cross-neutralize (in vitro) and cross-protect (in vivo) against the B.1.1.7 and B.1.351 VOCs was recently reported [14].…”

Systemic and Lower Respiratory Tract Immunity to SARS-CoV-2 Omicron and Variants in Pediatric Severe COVID-19 and Mis-C

“…Plasma and ET samples were evaluated in a qualified SARS-CoV-2 pseudovirion neutralization assay (PsVNA) using the SARS-CoV-2 WA1/2020 strain, 5 variants of concern (VOCs) [ S2). SARS-CoV-2 neutralizing activity measured by PsVNA correlated with PRNT (plaque reduction neutralization test with authentic SARS-CoV-2 virus) in previous studies [9][10][11].…”

“…Median time to ET sample collection from hospital admission was 64 h (interquartile range (IQR) 33, 97 h). None of the 10 hospitalized children were on chronic immunosuppressive drugs or chemotherapy and only one of them received IVIG without COVID-19 antibodies [9] prior to collection of paired ET/plasma samples. Neutralizing antibody responses in matched plasma and endotracheal aspirate supernatants were measured against the SARS-CoV-2 WA1/2020 strain, as well as against VOIs: Epsilon (B.…”

“…Neutralization assays were performed as previously described [3,9,12]. For the neutralization assay, 50 µL of SARS-CoV-2 S pseudovirions (counting ~200,000 relative light units) were pre-incubated with an equal volume of medium containing plasma at serial dilutions at room temperature for 1 h, then virus-antibody mixtures were added to 293T-ACE2-TMPRSS2 cells [11] in a 96-well plate.…”

Neutralisation of circulating SARS-CoV-2 delta and omicron variants by convalescent plasma and SARS-CoV-2 hyperimmune intravenous human immunoglobulins for treatment of COVID-19

“…For comparison, we also evaluated 10 CP from recovered COVID-19 patients and 17 IVIG preparations that were manufactured with prepandemic plasma units. 5 Seventeen prepandemic IVIG lots (2019-IGIV) were all negative in the PsVNA against either WA1/2020 or the two VOCs (figure 1A and online supplemental table S1). Ten individual COVID-19 CP showed heterogeneity of neutralisation titres against the WA1/2020 strain.…”