RT Journal Article
SR Electronic
T1 The functions of SARS-CoV-2 neutralizing and infection-enhancing antibodies in vitro and in mice and nonhuman primates
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.12.31.424729
DO 10.1101/2020.12.31.424729
A1 Li, Dapeng
A1 Edwards, Robert J
A1 Manne, Kartik
A1 Martinez, David R.
A1 Schäfer, Alexandra
A1 Alam, S. Munir
A1 Wiehe, Kevin
A1 Lu, Xiaozhi
A1 Parks, Robert
A1 Sutherland, Laura L.
A1 Oguin, Thomas H.
A1 McDanal, Charlene
A1 Perez, Lautaro G.
A1 Mansouri, Katayoun
A1 Gobeil, Sophie M. C.
A1 Janowska, Katarzyna
A1 Stalls, Victoria
A1 Kopp, Megan
A1 Cai, Fangping
A1 Lee, Esther
A1 Foulger, Andrew
A1 Hernandez, Giovanna E.
A1 Sanzone, Aja
A1 Tilahun, Kedamawit
A1 Jiang, Chuancang
A1 Tse, Longping V.
A1 Bock, Kevin W.
A1 Minai, Mahnaz
A1 Nagata, Bianca M.
A1 Cronin, Kenneth
A1 Gee-Lai, Victoria
A1 Deyton, Margaret
A1 Barr, Maggie
A1 Von Holle, Tarra
A1 Macintyre, Andrew N.
A1 Stover, Erica
A1 Feldman, Jared
A1 Hauser, Blake M.
A1 Caradonna, Timothy M.
A1 Scobey, Trevor D.
A1 Moody, M. Anthony
A1 Cain, Derek W.
A1 DeMarco, C. Todd
A1 Denny, Thomas N.
A1 Woods, Christopher W.
A1 Petzold, Elizabeth W.
A1 Schmidt, Aaron G.
A1 Teng, I-Ting
A1 Zhou, Tongqing
A1 Kwong, Peter D.
A1 Mascola, John R.
A1 Graham, Barney S.
A1 Moore, Ian N.
A1 Seder, Robert
A1 Andersen, Hanne
A1 Lewis, Mark G.
A1 Montefiori, David C.
A1 Sempowski, Gregory D.
A1 Baric, Ralph S.
A1 Acharya, Priyamvada
A1 Haynes, Barton F.
A1 Saunders, Kevin O.
YR 2021
UL http://biorxiv.org/content/early/2021/01/02/2020.12.31.424729.abstract
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.