Single-cell profiling of T and B cell repertoires following SARS-CoV-2 mRNA vaccine

JCI Insight. 2021 Dec 22;6(24):e153201. doi: 10.1172/jci.insight.153201.


mRNA vaccines for SARS-CoV-2 have shown exceptional clinical efficacy, providing robust protection against severe disease. However, our understanding of transcriptional and repertoire changes following full vaccination remains incomplete. We used scRNA-Seq and functional assays to compare humoral and cellular responses to 2 doses of mRNA vaccine with responses observed in convalescent individuals with asymptomatic disease. Our analyses revealed enrichment of spike-specific B cells, activated CD4+ T cells, and robust antigen-specific polyfunctional CD4+ T cell responses following vaccination. On the other hand, although clonally expanded CD8+ T cells were observed following both vaccination and natural infection, CD8+ T cell responses were relatively weak and variable. In addition, TCR gene usage was variable, reflecting the diversity of repertoires and MHC polymorphism in the human population. Natural infection induced expansion of CD8+ T cell clones that occupy distinct clusters compared to those induced by vaccination and likely recognize a broader set of viral antigens of viral epitopes presented by the virus not seen in the mRNA vaccine. Our study highlights a coordinated adaptive immune response in which early CD4+ T cell responses facilitate the development of the B cell response and substantial expansion of effector CD8+ T cells, together capable of contributing to future recall responses.

Keywords: Adaptive immunity; COVID-19; T cell receptor; T cells; Vaccines.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 2019-nCoV Vaccine mRNA-1273 / immunology*
  • 2019-nCoV Vaccine mRNA-1273 / therapeutic use
  • Adaptive Immunity / genetics
  • Adaptive Immunity / immunology
  • Adult
  • Aged
  • Antigens, Viral
  • B-Lymphocytes
  • BNT162 Vaccine / immunology*
  • BNT162 Vaccine / therapeutic use
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • COVID-19 / immunology*
  • COVID-19 / prevention & control
  • COVID-19 Vaccines / immunology
  • COVID-19 Vaccines / therapeutic use
  • Carrier State
  • Convalescence
  • Epitopes
  • Female
  • Humans
  • Immunity, Cellular / genetics
  • Immunity, Cellular / immunology*
  • Immunity, Humoral / genetics
  • Immunity, Humoral / immunology*
  • Immunogenicity, Vaccine
  • Immunologic Memory
  • Male
  • Middle Aged
  • RNA-Seq
  • SARS-CoV-2
  • Single-Cell Analysis
  • Spike Glycoprotein, Coronavirus / immunology
  • Th1 Cells
  • Th17 Cells
  • Vaccines, Synthetic / immunology
  • Vaccines, Synthetic / therapeutic use
  • Young Adult
  • mRNA Vaccines / immunology
  • mRNA Vaccines / therapeutic use


  • Antigens, Viral
  • COVID-19 Vaccines
  • Epitopes
  • Spike Glycoprotein, Coronavirus
  • Vaccines, Synthetic
  • mRNA Vaccines
  • spike protein, SARS-CoV-2
  • 2019-nCoV Vaccine mRNA-1273
  • BNT162 Vaccine