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

Kevin J. Kramer, Erin M. Wilfong, Kelsey Voss, Sierra M. 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, Jeffrey C. Rathmell (), Rachel H. Bonami (), Ivelin S. Georgiev () and Jonathan M. Irish ()
Additional contact information
Kevin J. Kramer: Vanderbilt University Medical Center
Erin M. Wilfong: Vanderbilt University Medical Center
Kelsey Voss: Vanderbilt University Medical Center
Sierra M. Barone: Vanderbilt University Medical Center
Andrea R. Shiakolas: Vanderbilt University Medical Center
Nagarajan Raju: Vanderbilt University Medical Center
Caroline E. Roe: Vanderbilt University Medical Center
Naveenchandra Suryadevara: Vanderbilt Vaccine Center
Lauren M. Walker: Vanderbilt University Medical Center
Steven C. Wall: Vanderbilt University Medical Center
Ariana Paulo: Vanderbilt University Medical Center
Samuel Schaefer: Human Immunology Discovery Initiative of the Vanderbilt Center for Immunobiology
Debolanle Dahunsi: Vanderbilt University Medical Center
Camille S. Westlake: Vanderbilt University Medical Center
James E. Crowe: Vanderbilt Vaccine Center
Robert H. Carnahan: Vanderbilt Vaccine Center
Jeffrey C. Rathmell: Vanderbilt University Medical Center
Rachel H. Bonami: Vanderbilt University Medical Center
Ivelin S. Georgiev: Vanderbilt University Medical Center
Jonathan M. Irish: Vanderbilt University Medical Center

Nature Communications, 2022, vol. 13, issue 1, 1-20

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-31142-5

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