Molecular analysis of a public cross-neutralizing antibody response to SARS-CoV-2

Meng Yuan, Yiquan Wang, Huibin Lv, Timothy J.C. Tan, Ian A. Wilson, Nicholas C. Wu

Research output: Contribution to journalArticlepeer-review


As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concerns (VOCs) continue to emerge, cross-neutralizing antibody responses become key toward next-generation design of a more universal COVID-19 vaccine. By analyzing published data from the literature, we report here that the combination of germline genes IGHV2-5/IGLV2-14 represents a public antibody response to the receptor-binding domain (RBD) that potently cross-neutralizes a broad range of VOCs, including Omicron and its sub-lineages. Detailed molecular analysis shows that the complementarity-determining region H3 sequences of IGHV2-5/IGLV2-14-encoded RBD antibodies have a preferred length of 11 amino acids and a conserved HxIxxI motif. In addition, these antibodies have a strong allelic preference due to an allelic polymorphism at amino acid residue 54 of IGHV2-5, which is located at the paratope. These findings have important implications for understanding cross-neutralizing antibody responses to SARS-CoV-2 and its heterogenicity at the population level as well as the development of a universal COVID-19 vaccine.

Original languageEnglish (US)
Article number111650
JournalCell Reports
Issue number7
StatePublished - Nov 15 2022


  • COVID-19
  • CP: Immunology
  • CP: Microbiology
  • SARS-CoV-2
  • allelic preference
  • broadly neutralizing
  • data mining
  • public antibody
  • sequence analysis
  • variants of concern

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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