tetano
Editor, Senior Moderator
Cell Rep
. 2023 May 3;42(5):112503.
doi: 10.1016/j.celrep.2023.112503. Online ahead of print. Fortuitous somatic mutations during antibody evolution endow broad neutralization against SARS-CoV-2 Omicron variants
Jianbo Wu[SUP] 1 [/SUP], Zhenguo Chen[SUP] 1 [/SUP], Yidan Gao[SUP] 1 [/SUP], Zegen Wang[SUP] 2 [/SUP], Jiarong Wang[SUP] 2 [/SUP], Bing-Yu Chiang[SUP] 2 [/SUP], Yunjiao Zhou[SUP] 3 [/SUP], Yuru Han[SUP] 1 [/SUP], Wuqiang Zhan[SUP] 1 [/SUP], Minxiang Xie[SUP] 1 [/SUP], Weiyu Jiang[SUP] 1 [/SUP], Xiang Zhang[SUP] 1 [/SUP], Aihua Hao[SUP] 1 [/SUP], Anqi Xia[SUP] 1 [/SUP], Jiaying He[SUP] 1 [/SUP], Song Xue[SUP] 1 [/SUP], Christian T Mayer[SUP] 4 [/SUP], Fan Wu[SUP] 1 [/SUP], Bin Wang[SUP] 5 [/SUP], Lunan Zhang[SUP] 6 [/SUP], Lei Sun[SUP] 7 [/SUP], Qiao Wang[SUP] 8 [/SUP]
Affiliations
Striking antibody evasion by emerging circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants drives the identification of broadly neutralizing antibodies (bNAbs). However, how a bNAb acquires increased neutralization breadth during antibody evolution is still elusive. Here, we identify a clonally related antibody family from a convalescent individual. One of the members, XG005, exhibits potent and broad neutralizing activities against SARS-CoV-2 variants, while the other members show significant reductions in neutralization breadth and potency, especially against the Omicron sublineages. Structural analysis visualizing the XG005-Omicron spike binding interface reveals how crucial somatic mutations endow XG005 with greater neutralization potency and breadth. A single administration of XG005 with extended half-life, reduced antibody-dependent enhancement (ADE) effect, and increased antibody product quality exhibits a high therapeutic efficacy in BA.2- and BA.5-challenged mice. Our results provide a natural example to show the importance of somatic hypermutation during antibody evolution for SARS-CoV-2 neutralization breadth and potency.
Keywords: CP: Immunology; CP: Microbiology; SARS-CoV-2; bNAb; broadly neutralizing antibody; clonally related antibody family; somatic hypermutation; variant of concern.
. 2023 May 3;42(5):112503.
doi: 10.1016/j.celrep.2023.112503. Online ahead of print. Fortuitous somatic mutations during antibody evolution endow broad neutralization against SARS-CoV-2 Omicron variants
Jianbo Wu[SUP] 1 [/SUP], Zhenguo Chen[SUP] 1 [/SUP], Yidan Gao[SUP] 1 [/SUP], Zegen Wang[SUP] 2 [/SUP], Jiarong Wang[SUP] 2 [/SUP], Bing-Yu Chiang[SUP] 2 [/SUP], Yunjiao Zhou[SUP] 3 [/SUP], Yuru Han[SUP] 1 [/SUP], Wuqiang Zhan[SUP] 1 [/SUP], Minxiang Xie[SUP] 1 [/SUP], Weiyu Jiang[SUP] 1 [/SUP], Xiang Zhang[SUP] 1 [/SUP], Aihua Hao[SUP] 1 [/SUP], Anqi Xia[SUP] 1 [/SUP], Jiaying He[SUP] 1 [/SUP], Song Xue[SUP] 1 [/SUP], Christian T Mayer[SUP] 4 [/SUP], Fan Wu[SUP] 1 [/SUP], Bin Wang[SUP] 5 [/SUP], Lunan Zhang[SUP] 6 [/SUP], Lei Sun[SUP] 7 [/SUP], Qiao Wang[SUP] 8 [/SUP]
Affiliations
- PMID: 37178120
- DOI: 10.1016/j.celrep.2023.112503
Striking antibody evasion by emerging circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants drives the identification of broadly neutralizing antibodies (bNAbs). However, how a bNAb acquires increased neutralization breadth during antibody evolution is still elusive. Here, we identify a clonally related antibody family from a convalescent individual. One of the members, XG005, exhibits potent and broad neutralizing activities against SARS-CoV-2 variants, while the other members show significant reductions in neutralization breadth and potency, especially against the Omicron sublineages. Structural analysis visualizing the XG005-Omicron spike binding interface reveals how crucial somatic mutations endow XG005 with greater neutralization potency and breadth. A single administration of XG005 with extended half-life, reduced antibody-dependent enhancement (ADE) effect, and increased antibody product quality exhibits a high therapeutic efficacy in BA.2- and BA.5-challenged mice. Our results provide a natural example to show the importance of somatic hypermutation during antibody evolution for SARS-CoV-2 neutralization breadth and potency.
Keywords: CP: Immunology; CP: Microbiology; SARS-CoV-2; bNAb; broadly neutralizing antibody; clonally related antibody family; somatic hypermutation; variant of concern.