Antibody engineering improves neutralization activity against K417 spike mutant SARS-CoV-2 variants

作者：Lili Li, Meiling Gao, Peng Jiao, Shulong Zu, Yong‐Qiang Deng, Dingyi Wan, Yang Cao, Jing Duan, Saba R. Aliyari, Jie Li, Yueyue Shi, Zihe Rao, Cheng‐Feng Qin, Yu Guo, Genhong Cheng, Heng Yang · 发表于：Cell & Bioscience · 年份：2022 · DOI：10.1186/s13578-022-00794-7 · 被引用次数：10 · 研究领域：SARS-CoV-2 and COVID-19 Research、Monoclonal and Polyclonal Antibodies Research、vaccines and immunoinformatics approaches

BACKGROUND: Neutralizing antibodies are approved drugs to treat coronavirus disease-2019 (COVID-19) patients, yet mutations in severe acute respiratory syndrome coronavirus (SARS-CoV-2) variants may reduce the antibody neutralizing activity. New monoclonal antibodies (mAbs) and antibody remolding strategies are recalled in the battle with COVID-19 epidemic. RESULTS: We identified multiple mAbs from antibody phage display library made from COVID-19 patients and further characterized the R3P1-E4 clone, which effectively suppressed SARS-CoV-2 infection and rescued the lethal phenotype in mice infected with SARS-CoV-2. Crystal structural analysis not only explained why R3P1-E4 had selectively reduced binding and neutralizing activity to SARS-CoV-2 variants carrying K417 mutations, but also allowed us to engineer mutant antibodies with improved neutralizing activity against these variants. Thus, we screened out R3P1-E4 mAb which inhibits SARS-CoV-2 and related mutations in vitro and in vivo. Antibody engineering improved neutralizing activity of R3P1-E4 against K417 mutations. CONCLUSION: Our studies have outlined a strategy to identify and engineer neutralizing antibodies against SARS-CoV-2 variants.