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

当前位置： X-MOL 学术 › Cell › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies
Cell ( IF 45.5 ) Pub Date : 2021-06-18 , DOI: 10.1016/j.cell.2021.06.021
Dapeng Li ₁ , Robert J Edwards ₁ , Kartik Manne ₁ , David R Martinez ₂ , Alexandra Schäfer ₂ , S Munir Alam ₁ , Kevin Wiehe ₁ , Xiaozhi Lu ₁ , Robert Parks ₁ , Laura L Sutherland ₁ , Thomas H Oguin ₁ , Charlene McDanal ₃ , Lautaro G Perez ₃ , Katayoun Mansouri ₁ , Sophie M C Gobeil ₁ , Katarzyna Janowska ₁ , Victoria Stalls ₁ , Megan Kopp ₁ , Fangping Cai ₁ , Esther Lee ₁ , Andrew Foulger ₁ , Giovanna E Hernandez ₁ , Aja Sanzone ₁ , Kedamawit Tilahun ₁ , Chuancang Jiang ₁ , Longping V Tse ₂ , Kevin W Bock ₄ , Mahnaz Minai ₄ , Bianca M Nagata ₄ , Kenneth Cronin ₁ , Victoria Gee-Lai ₁ , Margaret Deyton ₁ , Maggie Barr ₁ , Tarra Von Holle ₁ , Andrew N Macintyre ₁ , Erica Stover ₁ , Jared Feldman ₅ , Blake M Hauser ₅ , Timothy M Caradonna ₅ , Trevor D Scobey ₂ , Wes Rountree ₁ , Yunfei Wang ₁ , M Anthony Moody ₆ , Derek W Cain ₁ , C Todd DeMarco ₁ , Thomas N Denny ₁ , Christopher W Woods ₇ , Elizabeth W Petzold ₈ , Aaron G Schmidt ₉ , I-Ting Teng ₁₀ , Tongqing Zhou ₁₀ , Peter D Kwong ₁₁ , John R Mascola ₁₀ , Barney S Graham ₁₀ , Ian N Moore ₄ , Robert Seder ₁₀ , Hanne Andersen ₁₂ , Mark G Lewis ₁₂ , David C Montefiori ₃ , Gregory D Sempowski ₁ , Ralph S Baric ₂ , Priyamvada Acharya ₁₃ , Barton F Haynes ₁₄ , Kevin O Saunders ₁₅

Affiliation

Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Department of Surgery, Duke University, Durham, NC 27710, USA.
Infectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA.
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Center for Applied Genomics and Precision Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Center for Applied Genomics and Precision Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD 20892, USA.
Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD 20892, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
BIOQUAL, Rockville, MD 20850, USA.
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Surgery, Duke University, Durham, NC 27710, USA.
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Surgery, Duke University, Durham, NC 27710, USA; Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA.

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.

中文翻译：

SARS-CoV-2感染增强和中和抗体的体外和体内功能

SARS-CoV-2 中和抗体 (NAb) 可预防 COVID-19。关于 SARS-CoV-2 抗体的一个担忧是它们是否会介导疾病加重。在这里，我们从患有急性或恢复期 SARS-CoV-2 或有 SARS-CoV 感染史的个体中分离出针对 SARS-CoV-2 刺突的受体结合域 (RBD) 或 N 末端域 (NTD) 的 NAb。 RBD 和 NTD 抗体的冷冻电镜显示了功能特异性的结合模式。选择的 RBD NAb 还证明了 Fc 受体-γ (FcγR) 介导的体外病毒感染增强作用，而五种非中和性 NTD 抗体介导了不依赖于 FcγR 的体外感染增强作用。然而，这两种类型的感染增强抗体都能防止猴子和小鼠体内的 SARS-CoV-2 复制。与对照组相比，注射了增强抗体的 46 只猴子中，有 3 只的肺部炎症评分更高。一只猴子出现肺泡水肿，支气管肺泡灌洗液炎症细胞因子升高。因此，虽然体外抗体增强的感染并不一定预示着体内感染的增强，但在注射 SARS-CoV-2 抗体的猕猴中很少会出现肺部炎症增加。

更新日期：2021-08-05

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11