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DOI 10.1016/j.cell.2021.06.021

Медицинская библиотека · Cell · 2021

In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies.

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 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

СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПеревод пока не подготовлен

Аннотация

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.

Для цитирования: 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 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. In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies.. Cell. 2021. DOI: 10.1016/j.cell.2021.06.021.

Предметные рубрики MeSH

AnimalsAntibodies, NeutralizingAntibodies, ViralBronchoalveolar Lavage FluidCOVID-19CytokinesFemaleHaplorhiniHumansLungMaleMiceMice, Inbred BALB CProtein DomainsReceptors, IgGSARS-CoV-2Spike Glycoprotein, CoronavirusViral LoadVirus Replication
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