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

2021; Nature Portfolio; Volume: 27; Issue: 4 Linguagem: Inglês

10.1038/s41591-021-01294-w

1546-170X

Rita E. Chen, Xianwen Zhang, James Brett Case, Emma S. Winkler, Yang Liu, Laura A. VanBlargan, Jianying Liu, John M. Errico, Xuping Xie, Naveenchandra Suryadevara, Pavlo Gilchuk, Seth J. Zost, Stephen Tahan, Lindsay Droit, Jackson S. Turner, Wooseob Kim, Aaron J. Schmitz, Mahima Thapa, David Wang, Adrianus C. M. Boon, Rachel M. Presti, Jane A. O’Halloran, Alfred H.J. Kim, Parakkal Deepak, Dora Pinto, Daved H. Fremont, James E. Crowe, Davide Corti, Herbert W. Virgin, Ali H. Ellebedy, Pei‐Yong Shi, Michael Diamond,

Viral gastroenteritis research and epidemiology

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.