tetano
Editor, Senior Moderator
Nat Commun
. 2024 Aug 31;15(1):7585.
doi: 10.1038/s41467-024-51770-3. Antibodies utilizing VL6-57 light chains target a convergent cryptic epitope on SARS-CoV-2 spike protein and potentially drive the genesis of Omicron variants
Qihong Yan[SUP] #[/SUP][SUP] 1 [/SUP], Xijie Gao[SUP] #[/SUP][SUP] 2 [/SUP], Banghui Liu[SUP] #[/SUP][SUP] 3 [/SUP], Ruitian Hou[SUP] 4 [/SUP], Ping He[SUP] 5 [/SUP], Yong Ma[SUP] 3 [/SUP], Yudi Zhang[SUP] 3 6 [/SUP], Yanjun Zhang[SUP] 1 [/SUP], Zimu Li[SUP] 3 [/SUP], Qiuluan Chen[SUP] 7 [/SUP], Jingjing Wang[SUP] 3 [/SUP], Xiaohan Huang[SUP] 1 [/SUP], Huan Liang[SUP] 1 [/SUP], Huiran Zheng[SUP] 1 [/SUP], Yichen Yao[SUP] 8 [/SUP], Xianying Chen[SUP] 1 [/SUP], Xuefeng Niu[SUP] 1 [/SUP], Jun He[SUP] 9 [/SUP], Ling Chen[SUP] 10 11 12 [/SUP], Jincun Zhao[SUP] 13 14 15 [/SUP], Xiaoli Xiong[SUP] 16 [/SUP]
Affiliations
Continued evolution of SARS-CoV-2 generates variants to challenge antibody immunity established by infection and vaccination. A connection between population immunity and genesis of virus variants has long been suggested but its molecular basis remains poorly understood. Here, we identify a class of SARS-CoV-2 neutralizing public antibodies defined by their shared usage of VL6-57 light chains. Although heavy chains of diverse genotypes are utilized, convergent HCDR3 rearrangements have been observed among these public antibodies to cooperate with germline VL6-57 LCDRs to target a convergent epitope defined by RBD residues S371-S373-S375. Antibody repertoire analysis identifies that this class of VL6-57 antibodies is present in SARS-CoV-2-naive individuals and is clonally expanded in most COVID-19 patients. We confirm that Omicron-specific substitutions at S371, S373 and S375 mediate escape of antibodies of the VL6-57 class. These findings support that this class of public antibodies constitutes a potential immune pressure promoting the introduction of S371L/F-S373P-S375F in Omicron variants. The results provide further molecular evidence to support that antigenic evolution of SARS-CoV-2 is driven by antibody mediated population immunity.
. 2024 Aug 31;15(1):7585.
doi: 10.1038/s41467-024-51770-3. Antibodies utilizing VL6-57 light chains target a convergent cryptic epitope on SARS-CoV-2 spike protein and potentially drive the genesis of Omicron variants
Qihong Yan[SUP] #[/SUP][SUP] 1 [/SUP], Xijie Gao[SUP] #[/SUP][SUP] 2 [/SUP], Banghui Liu[SUP] #[/SUP][SUP] 3 [/SUP], Ruitian Hou[SUP] 4 [/SUP], Ping He[SUP] 5 [/SUP], Yong Ma[SUP] 3 [/SUP], Yudi Zhang[SUP] 3 6 [/SUP], Yanjun Zhang[SUP] 1 [/SUP], Zimu Li[SUP] 3 [/SUP], Qiuluan Chen[SUP] 7 [/SUP], Jingjing Wang[SUP] 3 [/SUP], Xiaohan Huang[SUP] 1 [/SUP], Huan Liang[SUP] 1 [/SUP], Huiran Zheng[SUP] 1 [/SUP], Yichen Yao[SUP] 8 [/SUP], Xianying Chen[SUP] 1 [/SUP], Xuefeng Niu[SUP] 1 [/SUP], Jun He[SUP] 9 [/SUP], Ling Chen[SUP] 10 11 12 [/SUP], Jincun Zhao[SUP] 13 14 15 [/SUP], Xiaoli Xiong[SUP] 16 [/SUP]
Affiliations
- PMID: 39217172
- PMCID: PMC11366018
- DOI: 10.1038/s41467-024-51770-3
Continued evolution of SARS-CoV-2 generates variants to challenge antibody immunity established by infection and vaccination. A connection between population immunity and genesis of virus variants has long been suggested but its molecular basis remains poorly understood. Here, we identify a class of SARS-CoV-2 neutralizing public antibodies defined by their shared usage of VL6-57 light chains. Although heavy chains of diverse genotypes are utilized, convergent HCDR3 rearrangements have been observed among these public antibodies to cooperate with germline VL6-57 LCDRs to target a convergent epitope defined by RBD residues S371-S373-S375. Antibody repertoire analysis identifies that this class of VL6-57 antibodies is present in SARS-CoV-2-naive individuals and is clonally expanded in most COVID-19 patients. We confirm that Omicron-specific substitutions at S371, S373 and S375 mediate escape of antibodies of the VL6-57 class. These findings support that this class of public antibodies constitutes a potential immune pressure promoting the introduction of S371L/F-S373P-S375F in Omicron variants. The results provide further molecular evidence to support that antigenic evolution of SARS-CoV-2 is driven by antibody mediated population immunity.