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

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  • Cell Biosci . Antibody engineering improves neutralization activity against K417 spike mutant SARS-CoV-2 variants


    Cell Biosci


    . 2022 May 17;12(1):63.
    doi: 10.1186/s13578-022-00794-7.
    Antibody engineering improves neutralization activity against K417 spike mutant SARS-CoV-2 variants


    Lili Li # 1 2 , Meiling Gao 1 2 , Peng Jiao 3 , Shulong Zu 1 2 , Yong-Qiang Deng 4 , Dingyi Wan 5 , Yang Cao 6 , Jing Duan 5 , Saba R Aliyari 7 , Jie Li 8 , Yueyue Shi 1 2 , Zihe Rao 3 9 , Cheng-Feng Qin 10 , Yu Guo 11 , Genhong Cheng 7 , Heng Yang 12 13



    Affiliations

    Abstract

    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.

    Keywords: Antibody engineering; COVID-19; Neutralizing antibody; Phage display library; SARS-CoV-2 variants.

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