Single-Cell Profiling of the Antigen-Specific Response to BNT162b2 SARS-CoV-2 RNA Vaccine

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 respons...

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Published inbioRxiv
Main Authors Kramer, Kevin J, Wilfong, Erin M, Voss, Kelsey, Barone, Sierra M, Shiakolas, Andrea R, Raju, Nagarajan, Roe, Caroline E, Suryadevara, Naveenchandra, Walker, Lauren, Wall, Steven C, Paulo, Ariana, Schaefer, Samuel, Dahunsi, Debolanle, Westlake, Camille S, Crowe, James E, Carnahan, Robert H, Rathmell, Jeffrey C, Bonami, Rachel H, Georgiev, Ivelin S, Irish, Jonathan M
Format Journal Article Paper
LanguageEnglish
Published United States Cold Spring Harbor Laboratory Press 28.07.2021
Subjects
Antigens
CD4 antigen
CD8 antigen
Coronaviruses
COVID-19
Cross-reactivity
Cytometry
Immunoglobulin A
Immunoglobulin G
Immunoglobulin M
Immunological memory
Learning algorithms
Lymphocytes B
Lymphocytes T
Memory cells
mRNA vaccines
Myositis
Proteomics
Ribonucleic acid
RNA
Severe acute respiratory syndrome coronavirus 2
Stockholders
Vaccines
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Summary: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. Single-cell profiling reveals the cellular basis of the antigen-specific response to the BNT162b2 SARS-CoV-2 RNA vaccine.
DOI:10.1101/2021.07.28.453981