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Germline IGHV3-53-encoded RBD-targeting neutralizing antibodies are commonly present in the antibody repertoires of COVID-19 patients
by
Li, Song
, Qu, Linbing
, Niu, Xuefeng
, Li, Pingchao
, Chen, Zhaoming
, Xiong, Xiaoli
, Li, Feng
, He, Ping
, Liu, Xinglong
, Feng, Liqiang
, Han, Jian
, Zhang, Yudi
, Luo, Kun
, Fan, Xiaodi
, Mo, Xiaoneng
, Yi, Haisu
, Wang, Qian
, Yan, Qihong
, Hou, Ruitian
, Liang, Huan
, Deng, Yijun
, Chen, Yunfei
, Huang, Xiaohan
, Chen, Ling
in
Antibodies
/ antibody repertoire sequencing
/ COVID-19
/ IGHV3-53
/ receptor-binding domain
/ SARS-CoV-2
/ Severe acute respiratory syndrome coronavirus 2
/ shared clonotype
2021
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Germline IGHV3-53-encoded RBD-targeting neutralizing antibodies are commonly present in the antibody repertoires of COVID-19 patients
by
Li, Song
, Qu, Linbing
, Niu, Xuefeng
, Li, Pingchao
, Chen, Zhaoming
, Xiong, Xiaoli
, Li, Feng
, He, Ping
, Liu, Xinglong
, Feng, Liqiang
, Han, Jian
, Zhang, Yudi
, Luo, Kun
, Fan, Xiaodi
, Mo, Xiaoneng
, Yi, Haisu
, Wang, Qian
, Yan, Qihong
, Hou, Ruitian
, Liang, Huan
, Deng, Yijun
, Chen, Yunfei
, Huang, Xiaohan
, Chen, Ling
in
Antibodies
/ antibody repertoire sequencing
/ COVID-19
/ IGHV3-53
/ receptor-binding domain
/ SARS-CoV-2
/ Severe acute respiratory syndrome coronavirus 2
/ shared clonotype
2021
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Germline IGHV3-53-encoded RBD-targeting neutralizing antibodies are commonly present in the antibody repertoires of COVID-19 patients
by
Li, Song
, Qu, Linbing
, Niu, Xuefeng
, Li, Pingchao
, Chen, Zhaoming
, Xiong, Xiaoli
, Li, Feng
, He, Ping
, Liu, Xinglong
, Feng, Liqiang
, Han, Jian
, Zhang, Yudi
, Luo, Kun
, Fan, Xiaodi
, Mo, Xiaoneng
, Yi, Haisu
, Wang, Qian
, Yan, Qihong
, Hou, Ruitian
, Liang, Huan
, Deng, Yijun
, Chen, Yunfei
, Huang, Xiaohan
, Chen, Ling
in
Antibodies
/ antibody repertoire sequencing
/ COVID-19
/ IGHV3-53
/ receptor-binding domain
/ SARS-CoV-2
/ Severe acute respiratory syndrome coronavirus 2
/ shared clonotype
2021
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Germline IGHV3-53-encoded RBD-targeting neutralizing antibodies are commonly present in the antibody repertoires of COVID-19 patients
Journal Article
Germline IGHV3-53-encoded RBD-targeting neutralizing antibodies are commonly present in the antibody repertoires of COVID-19 patients
2021
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Overview
Monoclonal antibodies (mAbs) encoded by IGHV3-53 (VH3-53) targeting the spike receptor-binding domain (RBD) have been isolated from different COVID-19 patients. However, the existence and prevalence of shared VH3-53-encoded antibodies in the antibody repertoires is not clear. Using antibody repertoire sequencing, we found that the usage of VH3-53 increased after SARS-CoV-2 infection. A highly shared VH3-53-J6 clonotype was identified in 9 out of 13 COVID-19 patients. This clonotype was derived from convergent gene rearrangements with few somatic hypermutations and was evolutionary conserved. We synthesized 34 repertoire-deduced novel VH3-53-J6 heavy chains and paired with a common IGKV1-9 light chain to produce recombinant mAbs. Most of these recombinant mAbs (23/34) possess RBD binding and virus-neutralizing activities, and recognize ACE2 binding site via the same molecular interface. Our computational analysis, validated by laboratory experiments, revealed that VH3-53 antibodies targeting RBD are commonly present in COVID-19 patients' antibody repertoires, indicating many people have germline-like precursor sequences to rapidly generate SARS-CoV-2 neutralizing antibodies. Moreover, antigen-specific mAbs can be digitally obtained through antibody repertoire sequencing and computational analysis.
Publisher
Taylor & Francis,Taylor & Francis Ltd,Taylor & Francis Group
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