Tracking of activated cTfh cells following sequential influenza vaccinations reveals transcriptional profile of clonotypes driving a vaccine-induced immune response

Jennifer Currenti; Joshua Simmons; Jared Oakes; Silvana Gaudieri; Christian M Warren; Rama Gangula; Eric Alves; Ramesh Ram; Shay Leary; Jesse D Armitage; Rita M Smith; Abha Chopra; Natasha B Halasa; Mark A Pilkinton; Spyros A Kalams

doi:10.3389/fimmu.2023.1133781

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Tracking of activated cTfh cells following sequential influenza vaccinations reveals transcriptional profile of clonotypes driving a vaccine-induced immune response

Jennifer Currenti, Joshua Simmons, Jared Oakes, Silvana Gaudieri, Christian M Warren, Rama Gangula, Eric Alves, Ramesh Ram, Shay Leary, Jesse D Armitage, …

Frontiers in immunology, Vol.14, Art. 1133781

2023

DOI: https://doi.org/10.3389/fimmu.2023.1133781

PMID: 37063867

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Abstract

Adult

B-Lymphocytes

Humans

Immunity

Influenza Vaccines

Influenza, Human - prevention & control

Vaccination

Introduction: A vaccine against influenza is available seasonally but is not 100% effective. A predictor of successful seroconversion in adults is an increase in activated circulating T follicular helper (cTfh) cells after vaccination. However, the impact of repeated annual vaccinations on long-term protection and seasonal vaccine efficacy remains unclear. Methods: In this study, we examined the T cell receptor (TCR) repertoire and transcriptional profile of vaccine-induced expanded cTfh cells in individuals who received sequential seasonal influenza vaccines. We measured the magnitude of cTfh and plasmablast cell activation from day 0 (d0) to d7 post-vaccination as an indicator of a vaccine response. To assess TCR diversity and T cell expansion we sorted activated and resting cTfh cells at d0 and d7 post-vaccination and performed TCR sequencing. We also single cell sorted activated and resting cTfh cells for TCR analysis and transcriptome sequencing. Results and discussion: The percent of activated cTfh cells significantly increased from d0 to d7 in each of the 2016-17 (p < 0.0001) and 2017-18 (p = 0.015) vaccine seasons with the magnitude of cTfh activation increase positively correlated with the frequency of circulating plasmablast cells in the 2016-17 (p = 0.0001) and 2017-18 (p = 0.003) seasons. At d7 post-vaccination, higher magnitudes of cTfh activation were associated with increased clonality of cTfh TCR repertoire. The TCRs from vaccine-expanded clonotypes were identified and tracked longitudinally with several TCRs found to be present in both years. The transcriptomic profile of these expanded cTfh cells at the single cell level demonstrated overrepresentation of transcripts of genes involved in the type-I interferon pathway, pathways involved in gene expression, and antigen presentation and recognition. These results identify the expansion and transcriptomic profile of vaccine-induced cTfh cells important for B cell help.

Details

Title: Tracking of activated cTfh cells following sequential influenza vaccinations reveals transcriptional profile of clonotypes driving a vaccine-induced immune response
Authors/Creators: Jennifer Currenti - The University of Western Australia
Joshua Simmons - Vanderbilt University Medical Center
Jared Oakes - Vanderbilt University Medical Center
Silvana Gaudieri - Murdoch University, Institute for Immunology and Infectious Diseases
Christian M Warren - Vanderbilt University Medical Center
Rama Gangula - Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
Eric Alves - School of Human Sciences, University of Western Australia, Crawley, WA, Australia
Ramesh Ram - Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, WA, Australia
Shay Leary - Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, WA, Australia
Jesse D Armitage - Telethon Kids Institute, University of Western Australia, Nedlands, WA, Australia
Rita M Smith - Vanderbilt University Medical Center
Abha Chopra - Murdoch University, Centre for Molecular Medicine and Innovative Therapeutics
Natasha B Halasa - Vanderbilt University Medical Center
Mark A Pilkinton - Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
Spyros A Kalams - Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, United States
Publication Details: Frontiers in immunology, Vol.14, Art. 1133781
Publisher: Frontiers Media SA
Grant note: P30 AI110527 / NIAID NIH HHS
Identifiers: 991005573470207891
Murdoch Affiliation: Institute for Immunology and Infectious Diseases
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.104 Virology - General; 1.104.126 Influenza
Web Of Science research areas: Immunology
ESI research areas: Immunology