PT  - JOURNAL ARTICLE
AU  - Dapeng Li
AU  - Robert J Edwards
AU  - Kartik Manne
AU  - David R. Martinez
AU  - Alexandra Schäfer
AU  - S. Munir Alam
AU  - Kevin Wiehe
AU  - Xiaozhi Lu
AU  - Robert Parks
AU  - Laura L. Sutherland
AU  - Thomas H. Oguin III
AU  - Charlene McDanal
AU  - Lautaro G. Perez
AU  - Katayoun Mansouri
AU  - Sophie M. C. Gobeil
AU  - Katarzyna Janowska
AU  - Victoria Stalls
AU  - Megan Kopp
AU  - Fangping Cai
AU  - Esther Lee
AU  - Andrew Foulger
AU  - Giovanna E. Hernandez
AU  - Aja Sanzone
AU  - Kedamawit Tilahun
AU  - Chuancang Jiang
AU  - Longping V. Tse
AU  - Kevin W. Bock
AU  - Mahnaz Minai
AU  - Bianca M. Nagata
AU  - Kenneth Cronin
AU  - Victoria Gee-Lai
AU  - Margaret Deyton
AU  - Maggie Barr
AU  - Tarra Von Holle
AU  - Andrew N. Macintyre
AU  - Erica Stover
AU  - Jared Feldman
AU  - Blake M. Hauser
AU  - Timothy M. Caradonna
AU  - Trevor D. Scobey
AU  - M. Anthony Moody
AU  - Derek W. Cain
AU  - C. Todd DeMarco
AU  - Thomas N. Denny
AU  - Christopher W. Woods
AU  - Elizabeth W. Petzold
AU  - Aaron G. Schmidt
AU  - I-Ting Teng
AU  - Tongqing Zhou
AU  - Peter D. Kwong
AU  - John R. Mascola
AU  - Barney S. Graham
AU  - Ian N. Moore
AU  - Robert Seder
AU  - Hanne Andersen
AU  - Mark G. Lewis
AU  - David C. Montefiori
AU  - Gregory D. Sempowski
AU  - Ralph S. Baric
AU  - Priyamvada Acharya
AU  - Barton F. Haynes
AU  - Kevin O. Saunders
TI  - The functions of SARS-CoV-2 neutralizing and infection-enhancing antibodies in vitro and in mice and nonhuman primates
AID  - 10.1101/2020.12.31.424729
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2020.12.31.424729
4099  - http://biorxiv.org/content/early/2021/01/02/2020.12.31.424729.short
4100  - http://biorxiv.org/content/early/2021/01/02/2020.12.31.424729.full
AB  - 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.Competing Interest StatementThe authors have declared no competing interest.