Single-Cell Profiling of the Antigen-Specific Response to BNT162b2 SARS-CoV-2 RNA Vaccine
Kevin J Kramer; Erin M Wilfong; Kelsey Voss; Sierra Barone; Andrea R Shiakolas; Nagarajan Raju; Caroline E Roe; Naveenchandra Suryadevara; Lauren M Walker; Steven C Wall; Ariana Paulo; Samuel Schaefer; Debolanle Dahunsi; Camille S. Westlake; James E. Crowe; Robert H Carnahan Jr.; Jeffrey C Rathmell; Rachel H Bonami; Ivelin S Georgiev; Jonathan Michael Irish.
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| PREPRINT-BIORXIV | ID: ppbiorxiv-453981
RNA-based vaccines against SARS-CoV-2 are critical to limiting COVID-19 severity and spread. Cellular mechanisms driving antigen-specific responses to these vaccines, however, remain uncertain. We used single-cell technologies to identify and characterized antigen-specific cells and antibody responses to the RNA vaccine BNT162b2 in longitudinal samples from a cohort of healthy donors. Mass cytometry and machine learning pinpointed a novel expanding, population of antigen-specific non-canonical memory CD4+ and CD8+ T cells. B cell sequencing suggested 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 correlated with eventual SARS-CoV-2 IgG and a donor lacking these cell populations failed to sustain SARS-CoV-2-specific antibodies and experienced breakthrough infection. These integrated proteomic and genomic platforms reveal an antigen-specific cellular basis of RNA vaccine-based immunity. ONE SENTENCE SUMMARYSingle-cell profiling reveals the cellular basis of the antigen-specific response to the BNT162b2 SARS-CoV-2 RNA vaccine.
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