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-Structure paper
タイトル | In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies. |
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ジャーナル・号・ページ | Cell, Vol. 184, Issue 16, Page 4203-4219.e32, Year 2021 |
掲載日 | 2021年8月5日 |
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 / Thomas N 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 / |
PubMed 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) 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. |
リンク | Cell / PubMed:34242577 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.97 - 19.3 Å |
構造データ | EMDB-22920: EMDB-22921: EMDB-22923: EMDB-22929: EMDB-22930: EMDB-22933: EMDB-22936: EMDB-22942: EMDB-22944: EMDB-22945: EMDB-22946: EMDB-22947: EMDB-22948: EMDB-22951: EMDB-22952: EMDB-22953: EMDB-22955: EMDB-22956: EMDB-22957: EMDB-22958: EMDB-22969: EMDB-22970: EMDB-22971: EMDB-22984: EMDB-22985: EMDB-22986: EMDB-23246: CryoEM map of SARS-CoV-2 S protein in complex with Receptor Binding Domain antibody DH1041 EMDB-23248: CryoEM map of SARS-CoV-2 S protein in complex with N-terminal domain antibody DH1052 EMDB-23277: CryoEM map of SARS-CoV-2 S protein in complex with N-terminal domain antibody DH1050.1 EMDB-23279: CryoEM map of SARS-CoV-2 S protein in complex with Receptor Binding Domain antibody DH1047 |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | VIRAL PROTEIN / IMMUNE SYSTEM / RBD antibody / DH1041 / SARS / COVID-19 / SARS-CoV-2 2P S ectodomain / DH1052 / DH1050.1 / DH1047 |