tetano
Editor, Senior Moderator
Nat Commun
. 2022 Jun 16;13(1):3466.
doi: 10.1038/s41467-022-31142-5.
Single-cell profiling of the antigen-specific response to BNT162b2 SARS-CoV-2 RNA vaccine
Kevin J Kramer[SUP] #[/SUP][SUP] 1 2 [/SUP], Erin M Wilfong[SUP] #[/SUP][SUP] 3 4 5 [/SUP], Kelsey Voss[SUP] #[/SUP][SUP] 1 [/SUP], Sierra M Barone[SUP] 1 6 7 [/SUP], Andrea R Shiakolas[SUP] 1 2 [/SUP], Nagarajan Raju[SUP] 1 2 [/SUP], Caroline E Roe[SUP] 1 6 7 [/SUP], Naveenchandra Suryadevara[SUP] 2 [/SUP], Lauren M Walker[SUP] 1 2 [/SUP], Steven C Wall[SUP] 1 2 [/SUP], Ariana Paulo[SUP] 1 2 [/SUP], Samuel Schaefer[SUP] 4 [/SUP], Debolanle Dahunsi[SUP] 1 4 [/SUP], Camille S Westlake[SUP] 3 [/SUP], James E Crowe Jr[SUP] 2 4 5 8 9 [/SUP], Robert H Carnahan[SUP] 2 [/SUP], Jeffrey C Rathmell[SUP] 10 11 12 13 14 [/SUP], Rachel H Bonami[SUP] 15 16 17 18 19 [/SUP], Ivelin S Georgiev[SUP] 20 21 22 23 24 [/SUP], Jonathan M Irish[SUP] 25 26 27 28 29 30 [/SUP]
Affiliations
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[SUP]+[/SUP] and CD8[SUP]+[/SUP] 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.
. 2022 Jun 16;13(1):3466.
doi: 10.1038/s41467-022-31142-5.
Single-cell profiling of the antigen-specific response to BNT162b2 SARS-CoV-2 RNA vaccine
Kevin J Kramer[SUP] #[/SUP][SUP] 1 2 [/SUP], Erin M Wilfong[SUP] #[/SUP][SUP] 3 4 5 [/SUP], Kelsey Voss[SUP] #[/SUP][SUP] 1 [/SUP], Sierra M Barone[SUP] 1 6 7 [/SUP], Andrea R Shiakolas[SUP] 1 2 [/SUP], Nagarajan Raju[SUP] 1 2 [/SUP], Caroline E Roe[SUP] 1 6 7 [/SUP], Naveenchandra Suryadevara[SUP] 2 [/SUP], Lauren M Walker[SUP] 1 2 [/SUP], Steven C Wall[SUP] 1 2 [/SUP], Ariana Paulo[SUP] 1 2 [/SUP], Samuel Schaefer[SUP] 4 [/SUP], Debolanle Dahunsi[SUP] 1 4 [/SUP], Camille S Westlake[SUP] 3 [/SUP], James E Crowe Jr[SUP] 2 4 5 8 9 [/SUP], Robert H Carnahan[SUP] 2 [/SUP], Jeffrey C Rathmell[SUP] 10 11 12 13 14 [/SUP], Rachel H Bonami[SUP] 15 16 17 18 19 [/SUP], Ivelin S Georgiev[SUP] 20 21 22 23 24 [/SUP], Jonathan M Irish[SUP] 25 26 27 28 29 30 [/SUP]
Affiliations
- PMID: 35710908
- DOI: 10.1038/s41467-022-31142-5
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[SUP]+[/SUP] and CD8[SUP]+[/SUP] 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.