tetano
Editor, Senior Moderator
Nat Commun
. 2022 May 2;13(1):2378.
doi: 10.1038/s41467-022-29950-w.
Unique binding pattern for a lineage of human antibodies with broad reactivity against influenza A virus
Xiaoyu Sun[SUP] #[/SUP][SUP] 1 [/SUP], Caixuan Liu[SUP] #[/SUP][SUP] 2 [/SUP], Xiao Lu[SUP] #[/SUP][SUP] 1 [/SUP], Zhiyang Ling[SUP] #[/SUP][SUP] 3 [/SUP], Chunyan Yi[SUP] #[/SUP][SUP] 1 [/SUP], Zhen Zhang[SUP] 1 [/SUP], Zi Li[SUP] 4 [/SUP], Mingliang Jin[SUP] 2 [/SUP], Wenshuai Wang[SUP] 1 [/SUP], Shubing Tang[SUP] 5 [/SUP], Fangfang Wang[SUP] 6 [/SUP], Fang Wang[SUP] 1 [/SUP], Sonam Wangmo[SUP] 1 7 [/SUP], Shuangfeng Chen[SUP] 1 7 [/SUP], Li Li[SUP] 7 [/SUP], Liyan Ma[SUP] 1 [/SUP], Yaguang Zhang[SUP] 1 [/SUP], Zhuo Yang[SUP] 1 [/SUP], Xiaoping Dong[SUP] 8 [/SUP], Zhikang Qian[SUP] 9 [/SUP], Jianping Ding[SUP] 1 [/SUP], Dayan Wang[SUP] 10 [/SUP], Yao Cong[SUP] 11 [/SUP], Bing Sun[SUP] 12 13 [/SUP]
Affiliations
Abstract
Most structurally characterized broadly neutralizing antibodies (bnAbs) against influenza A viruses (IAVs) target the conserved conformational epitopes of hemagglutinin (HA). Here, we report a lineage of naturally occurring human antibodies sharing the same germline gene, V[SUB]H[/SUB]3-48/V[SUB]K[/SUB]1-12. These antibodies broadly neutralize the major circulating strains of IAV in vitro and in vivo mainly by binding a contiguous epitope of H3N2 HA, but a conformational epitope of H1N1 HA, respectively. Our structural and functional studies of antibody 28-12 revealed that the continuous amino acids in helix A, particularly N49[SUB]HA2[/SUB] of H3 HA, are critical to determine the binding feature with 28-12. In contrast, the conformational epitope feature is dependent on the discontinuous segments involving helix A, the fusion peptide, and several HA1 residues within H1N1 HA. We report that this antibody was initially selected by H3 (group 2) viruses and evolved via somatic hypermutation to enhance the reactivity to H3 and acquire cross-neutralization to H1 (group 1) virus. These findings enrich our understanding of different antigenic determinants of heterosubtypic influenza viruses for the recognition of bnAbs and provide a reference for the design of influenza vaccines and more effective antiviral drugs.
. 2022 May 2;13(1):2378.
doi: 10.1038/s41467-022-29950-w.
Unique binding pattern for a lineage of human antibodies with broad reactivity against influenza A virus
Xiaoyu Sun[SUP] #[/SUP][SUP] 1 [/SUP], Caixuan Liu[SUP] #[/SUP][SUP] 2 [/SUP], Xiao Lu[SUP] #[/SUP][SUP] 1 [/SUP], Zhiyang Ling[SUP] #[/SUP][SUP] 3 [/SUP], Chunyan Yi[SUP] #[/SUP][SUP] 1 [/SUP], Zhen Zhang[SUP] 1 [/SUP], Zi Li[SUP] 4 [/SUP], Mingliang Jin[SUP] 2 [/SUP], Wenshuai Wang[SUP] 1 [/SUP], Shubing Tang[SUP] 5 [/SUP], Fangfang Wang[SUP] 6 [/SUP], Fang Wang[SUP] 1 [/SUP], Sonam Wangmo[SUP] 1 7 [/SUP], Shuangfeng Chen[SUP] 1 7 [/SUP], Li Li[SUP] 7 [/SUP], Liyan Ma[SUP] 1 [/SUP], Yaguang Zhang[SUP] 1 [/SUP], Zhuo Yang[SUP] 1 [/SUP], Xiaoping Dong[SUP] 8 [/SUP], Zhikang Qian[SUP] 9 [/SUP], Jianping Ding[SUP] 1 [/SUP], Dayan Wang[SUP] 10 [/SUP], Yao Cong[SUP] 11 [/SUP], Bing Sun[SUP] 12 13 [/SUP]
Affiliations
- PMID: 35501328
- DOI: 10.1038/s41467-022-29950-w
Abstract
Most structurally characterized broadly neutralizing antibodies (bnAbs) against influenza A viruses (IAVs) target the conserved conformational epitopes of hemagglutinin (HA). Here, we report a lineage of naturally occurring human antibodies sharing the same germline gene, V[SUB]H[/SUB]3-48/V[SUB]K[/SUB]1-12. These antibodies broadly neutralize the major circulating strains of IAV in vitro and in vivo mainly by binding a contiguous epitope of H3N2 HA, but a conformational epitope of H1N1 HA, respectively. Our structural and functional studies of antibody 28-12 revealed that the continuous amino acids in helix A, particularly N49[SUB]HA2[/SUB] of H3 HA, are critical to determine the binding feature with 28-12. In contrast, the conformational epitope feature is dependent on the discontinuous segments involving helix A, the fusion peptide, and several HA1 residues within H1N1 HA. We report that this antibody was initially selected by H3 (group 2) viruses and evolved via somatic hypermutation to enhance the reactivity to H3 and acquire cross-neutralization to H1 (group 1) virus. These findings enrich our understanding of different antigenic determinants of heterosubtypic influenza viruses for the recognition of bnAbs and provide a reference for the design of influenza vaccines and more effective antiviral drugs.