Neutralizing Antibodies to SARS-CoV-2 Selected from a Human Antibody Library Constructed Decades Ago.
Min QiangPeixiang MaYu LiHejun LiuAdam HardingChenyu MinFulian WangLili LiuMeng YuanQun JiPingdong TaoXiaojie ShiZhean LiTeng LiXian WangYu ZhangNicholas C WuChang-Chun David LeeXueyong ZhuJavier Gilbert JaramilloChuyue ZhangAbhishek SaxenaXingxu HuangHou WangWilliam S JamesRaymond A DwekIan A WilsonGuang YangRichard A LernerPublished in: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2021)
Combinatorial antibody libraries not only effectively reduce antibody discovery to a numbers game, but enable documentation of the history of antibody responses in an individual. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has prompted a wider application of this technology to meet the public health challenge of pandemic threats in the modern era. Herein, a combinatorial human antibody library constructed 20 years before the coronavirus disease 2019 (COVID-19) pandemic is used to discover three highly potent antibodies that selectively bind SARS-CoV-2 spike protein and neutralize authentic SARS-CoV-2 virus. Compared to neutralizing antibodies from COVID-19 patients with generally low somatic hypermutation (SHM), these three antibodies contain over 13-22 SHMs, many of which are involved in specific interactions in their crystal structures with SARS-CoV-2 spike receptor binding domain. The identification of these somatically mutated antibodies in a pre-pandemic library raises intriguing questions about the origin and evolution of these antibodies with respect to their reactivity with SARS-CoV-2.