In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies
Author(s) -
Dapeng Li,
Robert J. Edwards,
Kartik Manne,
David R. Martinez,
Alexandra Schäfer,
S. Munir Alam,
Kevin Wiehe,
Xiaozhi Lu,
Robert Parks,
Laura L. Sutherland,
Thomas H. Oguin,
Charlene McDanal,
Lautaro G. Perez,
Katayoun Mansouri,
S. Gobeil,
Katarzyna Janowska,
Victoria Stalls,
Megan Kopp,
Fangping Cai,
Esther Lee,
Andrew Foulger,
Giovanna E. Hernandez,
Aja Sanzone,
Kedamawit Tilahun,
Chuancang Jiang,
Longping V. Tse,
Kevin W. Bock,
Mahnaz Minai,
Bianca M. Nagata,
Kenneth Cronin,
Victoria Gee-Lai,
Margaret Deyton,
Maggie Barr,
Tarra Von Holle,
Andrew N. Macintyre,
Erica L. Stover,
Jared Feldman,
Blake M. Hauser,
Timothy M. Caradonna,
Trevor Scobey,
Wes Rountree,
Yunfei Wang,
M. Anthony Moody,
Derek W. Cain,
C. Todd DeMarco,
Thomas N. Denny,
Christopher W. Woods,
Elizabeth Petzold,
Aaron G. Schmidt,
ITing Teng,
Tongqing Zhou,
Peter D. Kwong,
John R. Mascola,
Barney S. Graham,
Ian N. Moore,
Robert A. Seder,
Hanné Andersen,
Mark G. Lewis,
David C. Montefiori,
Gregory D. Sempowski,
Ralph S. Baric,
Priyamvada Acharya,
Barton F. Haynes,
Kevin O. Saunders
Publication year - 2021
Publication title -
cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 26.304
H-Index - 776
eISSN - 1097-4172
pISSN - 0092-8674
DOI - 10.1016/j.cell.2021.06.021
Subject(s) - antibody , biology , in vivo , virology , immunology , in vitro , neutralizing antibody , inflammation , vero cell , antibody dependent enhancement , virus , bronchoalveolar lavage , receptor , lung , viral replication , medicine , biochemistry , microbiology and biotechnology
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) and 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.
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