National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01 AI145687
米国
引用
ジャーナル: bioRxiv / 年: 2021 タイトル: The functions of SARS-CoV-2 neutralizing and infection-enhancing antibodies in vitro and in mice and nonhuman primates. 著者: 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 ...著者: 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 / Sophie M C 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 Stover / Jared Feldman / Blake M Hauser / Timothy M Caradonna / Trevor D Scobey / Wes Rountree / Yunfei Wang / M Anthony Moody / Derek W Cain / C Todd DeMarco / ThomasN Denny / Christopher W Woods / Elizabeth W Petzold / Aaron G Schmidt / I-Ting Teng / Tongqing Zhou / Peter D Kwong / John R Mascola / Barney S Graham / Ian N Moore / Robert Seder / Hanne Andersen / Mark G Lewis / David C Montefiori / Gregory D Sempowski / Ralph S Baric / Priyamvada Acharya / Barton F Haynes / Kevin O Saunders 要旨: 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- ...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-1 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 , while five non-neutralizing NTD antibodies mediated FcγR-independent infection enhancement. However, both types of infection-enhancing antibodies protected from SARS-CoV-2 replication in monkeys and mice. Nonetheless, three of 31 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 antibody-enhanced infection does not necessarily herald enhanced infection , increased lung inflammation can occur in SARS-CoV-2 antibody-infused macaques.