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. Single-cell profiling of the antigen-specific response to BNT162b2 SARS-CoV-2 RNA vaccine. Nature communications. 2022 Dec 16;13(13). 3466 p. PMID: 35710908 [PubMed] PMCID: PMC9201272
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.