The functions of SARS-CoV-2 neutralizing and infection-enhancing antibodies in vitro and in mice and nonhuman primates.

BioRxiv : the Preprint Server for Biology
Dapeng LiKevin O Saunders

Abstract

SARS-CoV-2 neutralizing antibodies (NAbs) protect against COVID-19, making them a focus of vaccine design. A safety concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated potent NAbs against the receptor-binding domain (RBD) and the N-terminal domain (NTD) of SARS-CoV-2 spike protein from individuals with acute or convalescent SARS-CoV-2 or a history of SARS-CoV-1 infection. Cryo-electron microscopy of RBD and NTD antibodies demonstrated function-specific modes of antibody binding. Select RBD NAbs also demonstrated Fc receptor-γ (FcγR)-mediated enhancement of virus infection in vitro , while five non-neutralizing NTD antibodies mediated FcγR-independent in vitro infection enhancement. However, both in vitro neutralizing and infection-enhancing RBD or infection-enhancing NTD antibodies protected from SARS-CoV-2 challenge in non-human primates and mice. One of 30 monkeys infused with enhancing antibodies had lung pathology and bronchoalveolar lavage cytokine evidence suggestive of enhanced disease. Thus, these in vitro assessments of enhanced antibody-mediated infection do not necessarily indicate biologically relevant in vivo infection enhancement.

Citations

Mar 4, 2021·Nature Medicine·Constantinos Kurt WibmerPenny L Moore
Mar 26, 2021·Journal of Feline Medicine and Surgery·Alison E StoutGary R Whittaker
Apr 24, 2021·Microbial Cell Factories·Norma A Valdez-CruzMauricio A Trujillo-Roldán
Apr 21, 2021·MBio·Harini NatarajanMargaret E Ackerman
Jun 1, 2021·Virologica Sinica·Junwei LiYongxiang Yi
May 11, 2021·Nature·Kevin O SaundersBarton F Haynes

Methods Mentioned

BETA
electron microscopy
bronchoalveolar lavage
surface plasmon resonance
lavage

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