B cell receptor signatures associated with strong and poor SARS-CoV-2 vaccine responses

Emerg Microbes Infect. 2022 Dec;11(1):452-464. doi: 10.1080/22221751.2022.2030197.

Abstract

Breakthrough infection of SARS-CoV-2 is a serious challenge, as increased infections were documented in fully-vaccinated individuals. Recipients with poor antibody response are highly vulnerable to reinfection, whereas those with strong antibody responses achieve sterilizing immunity. Thus far, biomarkers associated with levels of vaccine-elicited antibody response are still lacking. Here, we studied the antibody response of age- and gender-controlled healthy cohort, who received inactivated SARS-CoV-2 vaccines and profiled the B cell receptor repertoires in longitudinally consecutive samples. Upon vaccination, all vaccinated individuals displayed a convergent antibody response with shared common antibody clones and public neutralizing antibodies. Strikingly, poor vaccine-responders are distinguishable from strong vaccine-responders by a biased V-usage before vaccination and IgG to IgM mRNA ratio. These findings reveal molecular signatures associated with the different levels of vaccine-induced antibody response, which could be further developed into biomarkers for the design of vaccination strategies.

Keywords: B cell receptor; COVID-19; SARS-CoV-2; antibody response; class switch recombination; inactivated vaccine.

MeSH terms

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines*
  • COVID-19*
  • Humans
  • Receptors, Antigen, B-Cell
  • SARS-CoV-2
  • Vaccination

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Receptors, Antigen, B-Cell

Grants and funding

This work was supported by the National Key R&D Program of China [2017YFA0506700 to F.L.M], National Natural Science Foundation of China [92169212 and 82041010 to W.Z; 31970880 to F.L.M; 31872744 to C.Q; 82002141 to J.A], Shanghai Science and Technology Committee [20490760200 to F.L.M; 20dz2210400 and 20dz2260100 to W.Z]. Chinese Academy of Sciences [JCTD-2020-17 to F.L.M and X.Z].