{"title":"A distinctive IGHV3-66 SARS-CoV-2 neutralizing antibody elicited by primary infection with an Omicron variant","authors":"Qing Fan, Congcong Liu, Huimin Guo, Shilong Tang, Haiyan Wang, Bing Zhou, Yuehong Sun, Miao Wang, Xiangyang Ge, Lei Liu, Bin Ju, Zheng Zhang","doi":"10.1016/j.str.2025.04.005","DOIUrl":null,"url":null,"abstract":"SARS-CoV-2 Omicron sub-variants continuously evolve under the pressure of neutralizing antibodies (nAbs), eliminating numerous potential elite monoclonal nAbs. The IGHV3-53/3-66 public nAbs have great potential for neutralizing SARS-CoV-2. However, it has been unclear whether a primary Omicron infection could also induce IGHV3-53/3-66 nAbs. In this study, we report an IGHV3-66-encoding monoclonal nAb, ConBA-998, that was elicited by primary infection with BA.1. ConBA-998 is an Omicron-dependent nAb with high binding affinity that triggers the shedding of the S1 subunit from the spike protein. The cryo-electron microscopy (cryo-EM) structure revealed the interactions between ConBA-998 and the Omicron BA.1 spike protein. ConBA-998 has a distinctive binding mode to receptor-binding domain (RBD) that differs from canonical IGHV3-53/3-66 nAbs. Overall, our findings indicate that Omicron may elicit unique specific nAbs distinct from those induced by pre-Omicron variants, providing further insights into SARS-CoV-2 variant-specific antibody responses.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"37 1","pages":""},"PeriodicalIF":4.3000,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Structure","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.str.2025.04.005","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
SARS-CoV-2 Omicron sub-variants continuously evolve under the pressure of neutralizing antibodies (nAbs), eliminating numerous potential elite monoclonal nAbs. The IGHV3-53/3-66 public nAbs have great potential for neutralizing SARS-CoV-2. However, it has been unclear whether a primary Omicron infection could also induce IGHV3-53/3-66 nAbs. In this study, we report an IGHV3-66-encoding monoclonal nAb, ConBA-998, that was elicited by primary infection with BA.1. ConBA-998 is an Omicron-dependent nAb with high binding affinity that triggers the shedding of the S1 subunit from the spike protein. The cryo-electron microscopy (cryo-EM) structure revealed the interactions between ConBA-998 and the Omicron BA.1 spike protein. ConBA-998 has a distinctive binding mode to receptor-binding domain (RBD) that differs from canonical IGHV3-53/3-66 nAbs. Overall, our findings indicate that Omicron may elicit unique specific nAbs distinct from those induced by pre-Omicron variants, providing further insights into SARS-CoV-2 variant-specific antibody responses.
期刊介绍:
Structure aims to publish papers of exceptional interest in the field of structural biology. The journal strives to be essential reading for structural biologists, as well as biologists and biochemists that are interested in macromolecular structure and function. Structure strongly encourages the submission of manuscripts that present structural and molecular insights into biological function and mechanism. Other reports that address fundamental questions in structural biology, such as structure-based examinations of protein evolution, folding, and/or design, will also be considered. We will consider the application of any method, experimental or computational, at high or low resolution, to conduct structural investigations, as long as the method is appropriate for the biological, functional, and mechanistic question(s) being addressed. Likewise, reports describing single-molecule analysis of biological mechanisms are welcome.
In general, the editors encourage submission of experimental structural studies that are enriched by an analysis of structure-activity relationships and will not consider studies that solely report structural information unless the structure or analysis is of exceptional and broad interest. Studies reporting only homology models, de novo models, or molecular dynamics simulations are also discouraged unless the models are informed by or validated by novel experimental data; rationalization of a large body of existing experimental evidence and making testable predictions based on a model or simulation is often not considered sufficient.