tetano
Editor, Senior Moderator
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[SUP] #[/SUP][SUP] 1 2 [/SUP], Meiling Gao[SUP] 1 2 [/SUP], Peng Jiao[SUP] 3 [/SUP], Shulong Zu[SUP] 1 2 [/SUP], Yong-Qiang Deng[SUP] 4 [/SUP], Dingyi Wan[SUP] 5 [/SUP], Yang Cao[SUP] 6 [/SUP], Jing Duan[SUP] 5 [/SUP], Saba R Aliyari[SUP] 7 [/SUP], Jie Li[SUP] 8 [/SUP], Yueyue Shi[SUP] 1 2 [/SUP], Zihe Rao[SUP] 3 9 [/SUP], Cheng-Feng Qin[SUP] 10 [/SUP], Yu Guo[SUP] 11 [/SUP], Genhong Cheng[SUP] 7 [/SUP], Heng Yang[SUP] 12 13 [/SUP]
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.
. 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[SUP] #[/SUP][SUP] 1 2 [/SUP], Meiling Gao[SUP] 1 2 [/SUP], Peng Jiao[SUP] 3 [/SUP], Shulong Zu[SUP] 1 2 [/SUP], Yong-Qiang Deng[SUP] 4 [/SUP], Dingyi Wan[SUP] 5 [/SUP], Yang Cao[SUP] 6 [/SUP], Jing Duan[SUP] 5 [/SUP], Saba R Aliyari[SUP] 7 [/SUP], Jie Li[SUP] 8 [/SUP], Yueyue Shi[SUP] 1 2 [/SUP], Zihe Rao[SUP] 3 9 [/SUP], Cheng-Feng Qin[SUP] 10 [/SUP], Yu Guo[SUP] 11 [/SUP], Genhong Cheng[SUP] 7 [/SUP], Heng Yang[SUP] 12 13 [/SUP]
Affiliations
- PMID: 35581593
- DOI: 10.1186/s13578-022-00794-7
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.