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.
Cell. 2021 Aug 5;184(16):4203-4219.e32. doi: 10.1016/j.cell.2021.06.021. Epub 2021 Jun 18.
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.
SARS-CoV-2 中和抗体（NAb）可预防 COVID-19。人们担心 SARS-CoV-2 抗体是否会介导疾病加重。在这里，我们从急性或恢复期 SARS-CoV-2 个体或 SARS-CoV 感染史个体中分离出针对刺突蛋白受体结合域（RBD）或 N 端结构域（NTD）的 NAb。RBD 和 NTD 抗体的冷冻电镜显示了功能特异性结合模式。一些选择的 RBD NAb 还显示了 Fc 受体γ（FcγR）介导的病毒感染在体外增强，而五种非中和 NTD 抗体介导了 FcγR 不依赖的体外感染增强。然而，这两种类型的感染增强抗体都能保护猴子和小鼠免受 SARS-CoV-2 复制的侵害。在输注增强抗体的 46 只猴子中，有 3 只的肺部炎症评分高于对照组。一只猴子出现肺泡水肿和支气管肺泡灌洗炎症细胞因子升高。因此，尽管体外抗体增强感染并不一定预示着体内感染增强，但在 SARS-CoV-2 抗体输注的猕猴中很少会发生肺部炎症增加。
