Technische Universität Braunschweig, Institut für Biochemie, Biotechnologie und Bioinformatik, Abteilung Biotechnologie, Braunschweig, Germany.
Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Nat Commun. 2021 Mar 11;12(1):1577. doi: 10.1038/s41467-021-21609-2.
COVID-19 is a severe acute respiratory disease caused by SARS-CoV-2, a new recently emerged sarbecovirus. This virus uses the human ACE2 enzyme as receptor for cell entry, recognizing it with the receptor binding domain (RBD) of the S1 subunit of the viral spike protein. We present the use of phage display to select anti-SARS-CoV-2 spike antibodies from the human naïve antibody gene libraries HAL9/10 and subsequent identification of 309 unique fully human antibodies against S1. 17 antibodies are binding to the RBD, showing inhibition of spike binding to cells expressing ACE2 as scFv-Fc and neutralize active SARS-CoV-2 virus infection of VeroE6 cells. The antibody STE73-2E9 is showing neutralization of active SARS-CoV-2 as IgG and is binding to the ACE2-RBD interface. Thus, universal libraries from healthy human donors offer the advantage that antibodies can be generated quickly and independent from the availability of material from recovering patients in a pandemic situation.
新型冠状病毒肺炎（COVID-19）是由新型严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）引起的急性呼吸道疾病。该病毒利用人体血管紧张素转换酶 2（ACE2）作为细胞进入受体，通过病毒刺突蛋白 S1 亚基的受体结合结构域（RBD）识别。我们使用噬菌体展示技术从人类原始抗体基因文库 HAL9/10 中筛选出抗 SARS-CoV-2 刺突蛋白的抗体，并随后鉴定出 309 种针对 S1 的独特全人源抗体。其中 17 种抗体可与 RBD 结合，以 scFv-Fc 的形式抑制刺突蛋白与表达 ACE2 的细胞结合，并中和活性 SARS-CoV-2 对 VeroE6 细胞的感染。抗体 STE73-2E9 可作为 IgG 中和活性 SARS-CoV-2，且可与 ACE2-RBD 界面结合。因此，来自健康人类供体的通用文库具有优势，可在大流行情况下，无需依赖恢复期患者的材料，快速且独立地产生抗体。
