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

Abstract

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.

Single-cell RNA sequencing to decipher the immunogenicity of ChAdOx1 nCoV-19/AZD1222 and mRNA-1273 vaccines in patients with autoimmune rheumatic diseases

“…demonstrated increasing spike-specific B cells, antigen-specific CD4 + T cells, and CD8 + T cells by scRNA-seq analysis in healthy subjects after mRNA vaccines and those after COVID-19 infection ( 31 ). Kramer KJ and the colleagues focused on adaptive immunity and indicated enlarged population of antigen-specific memory CD4+ and CD8+ T cells, and IgA and IgG memory B cells specific to SARS-CoV-2 in healthy participants after BNT162b2 mRNA vaccines ( 32 ). Those studies highlighted the importance of antigen presentation and antibodies productions following mRNA vaccines in healthy individuals.…”

COVID‐19 and plasma cells: Is there long‐lived protection?*

“… 264 , 265 A mass cytometry‐based study identified expansion of metabolically active, class‐switched plasmablasts expressing CD71, CD98, and cytochrome C between day 0 and 28 post‐vaccine. 266 Similarly, Amanat et al 128 reported that some of the isolated S2‐specific mAbs had cross‐reactivity toward human coronaviruses, suggestive of recall responses which were initially induced by seasonal beta‐coronavirus exposure. To support this model, some of the cross‐reactive mAbs showed extensive SHM.…”

“…Studies have shown that the first dose generated polyclonal non‐neutralizing IgA‐dominant ASC response with some S2‐specific plasmablasts with low SHM, whereas the second dose provided neutralizing B cell responses to S1 with RBD 264,265 . A mass cytometry‐based study identified expansion of metabolically active, class‐switched plasmablasts expressing CD71, CD98, and cytochrome C between day 0 and 28 post‐vaccine 266 . Similarly, Amanat et al 128 reported that some of the isolated S2‐specific mAbs had cross‐reactivity toward human coronaviruses, suggestive of recall responses which were initially induced by seasonal beta‐coronavirus exposure.…”

Comparative multi-OMICS single cell atlas of five COVID-19 (rAdVV and mRNA) vaccines describe unique and distinct mechanisms of action

“…In the past two years, several longitudinal studies have offered insights into the immune mechanisms following SARS-CoV-2 infection and/or vaccination, applying single-cell genomics, mass cytometry and flow cytometry methods [24][25][26][27] . The notion is that higher granularity analysis of molecular programs may illuminate issues such as difference in immunogenicity, efficacy, immune subsets and durability.…”