Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies

TLDR

SARS‑CoV‑2 has caused a global pandemic, and rapidly spreading variants threaten the effectiveness of newly introduced antibody and vaccine countermeasures. The study seeks to determine whether updated monoclonal antibody cocktails, increased potency, or vaccine spike modifications are needed to preserve protection against emerging variants with reduced neutralization. The authors evaluated neutralization of authentic and chimeric SARS‑CoV‑2 variants—including B.1.1.7, South African and Brazilian spike chimeras—using monoclonal antibodies, animal immune sera, convalescent sera, and sera from BNT162b2 vaccine recipients. Neutralization by many potent RBD‑ or NTD‑targeting monoclonal antibodies, convalescent sera, and vaccine‑induced sera was markedly reduced against variants carrying the E484K mutation, especially the B.1.351 isolate first identified in South Africa.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global COVID-19 pandemic. Rapidly spreading SARS-CoV-2 variants may jeopardize newly introduced antibody and vaccine countermeasures. Here, using monoclonal antibodies (mAbs), animal immune sera, human convalescent sera and human sera from recipients of the BNT162b2 mRNA vaccine, we report the impact on antibody neutralization of a panel of authentic SARS-CoV-2 variants including a B.1.1.7 isolate, chimeric strains with South African or Brazilian spike genes and isogenic recombinant viral variants. Many highly neutralizing mAbs engaging the receptor-binding domain or N-terminal domain and most convalescent sera and mRNA vaccine-induced immune sera showed reduced inhibitory activity against viruses containing an E484K spike mutation. As antibodies binding to spike receptor-binding domain and N-terminal domain demonstrate diminished neutralization potency in vitro against some emerging variants, updated mAb cocktails targeting highly conserved regions, enhancement of mAb potency or adjustments to the spike sequences of vaccines may be needed to prevent loss of protection in vivo. A comprehensive analysis of antibody neutralization activity against a panel of authentic isolates and chimeric SARS-CoV-2 variants shows markedly diminished neutralizing activity against the variant B.1.351, first identified in South Africa.