Single-cell profiling of the antigen-specific response to BNT162b2 SARS-CoV-2 RNA vaccine.

Journal Article (Journal Article)

RNA-based vaccines against SARS-CoV-2 have proven critical to limiting COVID-19 disease severity and spread. Cellular mechanisms driving antigen-specific responses to these vaccines, however, remain uncertain. Here we identify and characterize antigen-specific cells and antibody responses to the RNA vaccine BNT162b2 using multiple single-cell technologies for in depth analysis of longitudinal samples from a cohort of healthy participants. Mass cytometry and unbiased machine learning pinpoint an expanding, population of antigen-specific memory CD4+ and CD8+ T cells with characteristics of follicular or peripheral helper cells. B cell receptor sequencing suggest progression from IgM, with apparent cross-reactivity to endemic coronaviruses, to SARS-CoV-2-specific IgA and IgG memory B cells and plasmablasts. Responding lymphocyte populations correlate with eventual SARS-CoV-2 IgG, and a participant lacking these cell populations failed to sustain SARS-CoV-2-specific antibodies and experienced breakthrough infection. These integrated proteomic and genomic platforms identify an antigen-specific cellular basis of RNA vaccine-based immunity.

Full Text

Duke Authors

Cited Authors

  • Kramer, KJ; Wilfong, EM; Voss, K; Barone, SM; Shiakolas, AR; Raju, N; Roe, CE; Suryadevara, N; Walker, LM; Wall, SC; Paulo, A; Schaefer, S; Dahunsi, D; Westlake, CS; Crowe, JE; Carnahan, RH; Rathmell, JC; Bonami, RH; Georgiev, IS; Irish, JM

Published Date

  • June 16, 2022

Published In

Volume / Issue

  • 13 / 1

Start / End Page

  • 3466 -

PubMed ID

  • 35710908

Pubmed Central ID

  • PMC9201272

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-022-31142-5


  • eng

Conference Location

  • England