| 论文编号: |
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| 第一作者所在部门: |
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| 中文论文题目: |
Shared IGHV1-69-encoded neutralizing antibodies contribute to the emergence of L452R substitution in SARS-CoV-2 variants |
| 英文论文题目: |
Shared IGHV1-69-encoded neutralizing antibodies contribute to the emergence of L452R substitution in SARS-CoV-2 variants |
| 作者: |
Qihong Yan , Ruitian Hou , Xiaohan Huang , Yanjun Zhang , Ping He , Yudi Zhang , Banghui Liu , Qian Wang , Haiyue Rao , Xianying Chen , Xinwei Zhao , Xuefeng Niu , Jincun Zhao , Xiaoli Xiong , Ling Chen |
| 论文出处: |
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| 刊物名称: |
Emerging Microbes & Infections |
| 年: |
2022 |
| 卷: |
11 |
| 期: |
1 |
| 页: |
2749-2761 |
| 联系作者: |
Ling Chen |
| 收录类别: |
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| 影响因子: |
19.568 |
| 摘要: |
SARS-CoV-2 variants continue to emerge facing established herd immunity. L452R, previously featured in the Delta variant, quickly emerged in Omicron subvariants, including BA.4/BA.5, implying a continued selection pressure on this residue. The underlying links between spike mutations and their selective pressures remain incompletely understood. Here, by analyzing 221 structurally characterized antibodies, we found that IGHV1-69-encoded antibodies preferentially contact L452 using germline-encoded hydrophobic residues at the tip of HCDR2 loop. Whereas somatic hypermutations or VDJ rearrangements are required to acquire L452-contacting hydrophobic residues for non-IGHV1-69 encoded antibodies. Antibody repertoire analysis revealed that IGHV1-69 L452-contacting antibody lineages are commonly induced among COVID-19 convalescents but non-IGHV1-69 encoded antibodies exhibit limited prevalence. In addition, we experimentally demonstrated that L452R renders most published IGHV1-69 antibodies ineffective. Furthermore, we found that IGHV1-69 L452-contacting antibodies are enriched in convalescents experienced Omicron BA.1 (without L452R) breakthrough infections but rarely found in Delta (with L452R) breakthrough infections. Taken together, these findings support that IGHV1-69 population antibodies contribute to selection pressure for L452 substitution. This study thus provides a better understanding of SARS-CoV-2 variant genesis and immune evasion. |
| 英文摘要: |
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