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