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 o...

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Bibliographic Details
Published in:	Cell Vol. 184; no. 16; p. 4203
Main Authors:	Li, Dapeng, Edwards, Robert J, Manne, Kartik, Martinez, David R, Schäfer, Alexandra, Alam, S Munir, Wiehe, Kevin, Lu, Xiaozhi, Parks, Robert, Sutherland, Laura L, Oguin, 3rd, Thomas H, McDanal, Charlene, Perez, Lautaro G, Mansouri, Katayoun, Gobeil, Sophie M C, Janowska, Katarzyna, Stalls, Victoria, Kopp, Megan, Cai, Fangping, Lee, Esther, Foulger, Andrew, Hernandez, Giovanna E, Sanzone, Aja, Tilahun, Kedamawit, Jiang, Chuancang, Tse, Longping V, Bock, Kevin W, Minai, Mahnaz, Nagata, Bianca M, Cronin, Kenneth, Gee-Lai, Victoria, Deyton, Margaret, Barr, Maggie, Von Holle, Tarra, Macintyre, Andrew N, Stover, Erica, Feldman, Jared, Hauser, Blake M, Caradonna, Timothy M, Scobey, Trevor D, Rountree, Wes, Wang, Yunfei, Moody, M Anthony, Cain, Derek W, DeMarco, C Todd, Denny, Thomas N, Woods, Christopher W, Petzold, Elizabeth W, Schmidt, Aaron G, Teng, I-Ting, Zhou, Tongqing, Kwong, Peter D, Mascola, John R, Graham, Barney S, Moore, Ian N, Seder, Robert, Andersen, Hanne, Lewis, Mark G, Montefiori, David C, Sempowski, Gregory D, Baric, Ralph S, Acharya, Priyamvada, Haynes, Barton F, Saunders, Kevin O
Format:	Journal Article
Language:	English
Published:	United States 05.08.2021
Subjects:	Animals Antibodies, Neutralizing - immunology Antibodies, Viral - immunology Bronchoalveolar Lavage Fluid - chemistry COVID-19 - pathology COVID-19 - virology Cytokines - metabolism Female Haplorhini Humans Lung - pathology Lung - virology Male Mice Mice, Inbred BALB C Protein Domains Receptors, IgG - metabolism SARS-CoV-2 - isolation & purification SARS-CoV-2 - physiology Spike Glycoprotein, Coronavirus - chemistry Spike Glycoprotein, Coronavirus - immunology Viral Load Virus Replication COVID-19 electron micrograph SARS-CoV-2 cross-neutralization receptor-binding domain neutralizing antibody N-terminal domain antibody-dependent enhancement infection enhancement in vivo protection
ISSN:	1097-4172, 1097-4172
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1097-4172 1097-4172
DOI:	10.1016/j.cell.2021.06.021