The prominent role of a CDR1 somatic hypermutation for convergent IGHV3-53/3-66 antibodies in binding to SARS-CoV-2

Emerg Microbes Infect. 2022 Dec;11(1):1186-1190. doi: 10.1080/22221751.2022.2063074.

Abstract

In the fight against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), monoclonal antibodies (mAbs) serve as key strategies for the rapid prevention and treatment of COVID-19. However, analysis to fully characterize functional SARS-CoV-2 mAbs is still needed. In this study, by interrogating 1,695 published or patented mAbs of human origin and validated SARS-CoV-2-binding potency, we found a highly preferential usage of IGHV3-53/3-66 germline genes that was then revealed as a distinct selectivity of SARS-CoV-2-induced humoral immunity across other coronaviruses. Moreover, among the rare somatic hypermutations, we identified a novel mutation signature of F27 to I, L, or V with high frequency, which was located in the CDR1 region of the heavy chain among IGHV3-53/3-66-encoded antibodies. This convergent mutation contributed to improving SARS-CoV-2 binding affinity and may advance our knowledge of the humoral immunity to SARS-CoV-2.

Keywords: IGHV3-53/3-66; SARS-CoV-2; antibody affinity; monoclonal antibody; somatic hypermutation.

Publication types

  • Letter

MeSH terms

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19*
  • Humans
  • Immunity, Humoral
  • SARS-CoV-2* / genetics
  • Spike Glycoprotein, Coronavirus

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2

Grants and funding

This work was supported by grants from the National Key R&D Program of China [grant number 2019YFA0904400], and National Key Research and Development Program of China [grant numbers 81822027, 81630090, 81902108, 81974302].