Kramer KJ, Wilfong EM, Voss K, Barone SM, Shiakolas AR, Raju N, Roe CE, Suryadevara N, Walker L, 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. BioRxiv : the preprint server for biology. 2021 Jul. PMID: 34341788 [PubMed] PMCID: PMC8328055
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.