In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies.

SARS-CoV-2-neutralizing antibodies (NAbs) protect against COVID-19. A concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated NAbs against the receptor-binding domain (RBD) or the N-terminal domain (NTD) of SARS-CoV-2 spike from individuals with acute or convalescent SARS-CoV-2 or a history of SARS-CoV infection. Cryo-electron microscopy of RBD and NTD antibodies demonstrated function-specific modes of 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 types of infection-enhancing antibodies protected from SARS-CoV-2 replication in monkeys and mice. Three of 46 monkeys infused with enhancing antibodies had higher lung inflammation scores compared to controls. One monkey had alveolar edema and elevated bronchoalveolar lavage inflammatory cytokines. Thus, while in vitro antibody-enhanced infection does not necessarily herald enhanced infection in vivo, increased lung inflammation can rarely occur in SARS-CoV-2 antibody-infused macaques.

Duke Scholars

Author S. Munir Alam Medicine, Duke Human Vaccine Institute

Author Kevin J Wiehe Medicine, Duke Human Vaccine Institute

Author Andrew Neil Macintyre Medicine, Duke Human Vaccine Institute

Author Michael Anthony Moody Pediatrics, Infectious Diseases

Author Derek Wilson Cain Medicine, Duke Human Vaccine Institute

Author Thomas Norton Denny Medicine, Duke Human Vaccine Institute

Author Christopher Wildrick Woods Medicine, Infectious Diseases

Author David Charles Montefiori Surgery, Surgical Sciences

Author Priyamvada Acharya Surgery, Surgical Sciences

Author Barton Ford Haynes Medicine, Duke Human Vaccine Institute

Author Kevin O'Neil Saunders Surgery, Surgical Sciences