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TitleRapid clonal expansion and somatic hypermutation contribute to the fate of SARS-CoV-2 broadly neutralizing antibodies.
Journal, issue, pagesJ Immunol, Vol. 214, Issue 2, Page 278-289, Year 2025
Publish dateFeb 1, 2025
AuthorsMiao Wang / Congcong Liu / Qing Fan / Yuehong Sun / Shilong Tang / Huimin Guo / Bing Zhou / Haiyan Wang / Xiangyang Ge / Zheng Zhang / Bin Ju /
PubMed AbstractSeveral vaccines and immunization strategies, including inactivated vaccines, have proven effective in eliciting antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ...Several vaccines and immunization strategies, including inactivated vaccines, have proven effective in eliciting antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), providing an opportunity to characterize the antibody response. In this study, we investigated the monoclonal antibody responses elicited by wild-type SARS-CoV-2 inactivated vaccination compared to those elicited by natural infection and mRNA vaccination. The analysis showed that antibodies encoded by biased germline genes were shared between SARS-CoV-2 vaccinated and naturally infected individuals. Among the 35 shared clonotypes identified, besides the well-known IGHV3-53 and IGHV1-58, we identified a class of IGHV4-59 antibodies characterized by rapid response and neutralizing activity, elicited by 3 doses of inactivated vaccine. Members of this lineage exhibited similar sensitivity against wild-type SARS-CoV-2, whereas different neutralizing activities against SARS-CoV-2 variants, especially against various Omicron subvariants, BA.1, BA.2, BA.2.12.1, BA.4/5, and BA.2.75. Structural analysis of BA.1 spike complexed with VacBB-639 revealed that the IGHV4-59-lineage antibodies belonged to the Class 2/3 group. Using sequence alignment, site-mutation assays, and functional verification, we identified two substitutions, N60K in HFR3 and S56G in HCDR2, contributing to opposite neutralization changes of IGHV4-59-lineage antibodies against these Omicron subvariants. These results demonstrate the importance of somatic hypermutation in the evolution of prototypical antigen-elicited antibodies in terms of their neutralization breadth and potency against SARS-CoV-2 Omicron variants.
External linksJ Immunol / PubMed:40073246
MethodsEM (single particle)
Resolution4.19 Å
Structure data

38610

8xrq

EMDB-38610, PDB-8xrq:
SARS-CoV-2 BA.1 spike RBD in complex bound with VacBB-639
Method: EM (single particle) / Resolution: 4.19 Å

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsPROTEIN BINDING / Antibody / VIRAL PROTEIN-IMMUNE SYSTEM COMPLEX

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