CD11a and CD49d enhance the detection of antigen-specific T cells following human vaccination

Allison F Christiaansen; Upasna Gaur Dixit; Rhea N Coler; Anna Marie  Beckmann; Steven G Reed; Patricia L Winokur; M. Bridget Zimmerman; Steven M Varga; Mary E Wilson

doi:10.1016/j.vaccine.2017.06.013

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CD11a and CD49d enhance the detection of antigen-specific T cells following human vaccination

Journal article

Open access

Peer reviewed

CD11a and CD49d enhance the detection of antigen-specific T cells following human vaccination

Allison F Christiaansen, Upasna Gaur Dixit, Rhea N Coler, Anna Marie Beckmann, Steven G Reed, Patricia L Winokur, M. Bridget Zimmerman, Steven M Varga and Mary E Wilson

Vaccine, Vol.35(33), pp.4255-4261

07/24/2017

DOI: 10.1016/j.vaccine.2017.06.013

PMCID: PMC5551405

PMID: 28662951

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Abstract

Determining the efficacy of human vaccines that induce antigen-specific protective CD4 T cell responses against pathogens can be particularly challenging to evaluate. Surface expression of CD11a and CD49d has been shown to identify antigen-specific CD4 T cells against viral pathogens in mice. We hypothesized that CD11a and CD49d would also serve as markers of human antigen-specific T cells responding to vaccination. A phase I vaccine trial enabled us to evaluate a novel gating strategy based on surface expression of CD11a and CD49d as a means of detecting antigen-specific, cytokine producing CD4 and CD8 T cells induced after vaccination of naïve individuals against leishmaniasis. Three study groups received LEISH-F3 recombinant protein combined with either squalene oil-in-water emulsion (SE) alone, SE with the synthetic TLR-4 ligand glucopyranosyl lipid adjuvant (GLA-SE), or SE with Salmonella minnesota-derived monophosphoryl lipid A (MPL-SE). Individuals were given 3 vaccine doses, on days 0, 28 and 168. Starting after the first vaccine dose, the frequency of both CD11ahiCD49d+ CD4 and CD11ahiCD49d+ CD8 T cells significantly increased over time throughout the 24-week trial. To confirm the role of CD11ahiCD49d+ expression in the identification of the antigen-specific T cells, cytokine production was measured following LEISH-F3 stimulation. All of the IFN-γ, TNF-α, and IL-2 producing cells were found within the CD11ahiCD49d+ population. Our results suggest that the change in the frequency of CD11ahiCD49d+ T cells can be used to track antigen-specific CD4 and CD8 T cell responses following T cell-targeted vaccination.

Adjuvant

Protective immunity

Visceral leishmaniasis

Activation markers

T cell response

Details

Title: Subtitle: CD11a and CD49d enhance the detection of antigen-specific T cells following human vaccination
Creators: Allison F Christiaansen - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA
Upasna Gaur Dixit - Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA
Rhea N Coler - Infectious Disease Research Institute, Seattle, WA 98102, USA
Anna Marie Beckmann - Infectious Disease Research Institute, Seattle, WA 98102, USA
Steven G Reed - Infectious Disease Research Institute, Seattle, WA 98102, USA
Patricia L Winokur - Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA
M. Bridget Zimmerman - Department of Biostatistics, University of Iowa, Iowa City, IA 52242, USA
Steven M Varga - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA
Mary E Wilson - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Vaccine, Vol.35(33), pp.4255-4261
DOI: 10.1016/j.vaccine.2017.06.013
PMID: 28662951
PMCID: PMC5551405
NLM abbreviation: Vaccine
ISSN: 0264-410X
eISSN: 1873-2518
Publisher: Elsevier Ltd
Grant note: name: NIH Vaccine Trials and Evaluation Unit, award: HHSN272200800008C; DOI: 10.13039/100000865, name: Bill & Melinda Gates Foundation, award: #39129, OPP1055855
Language: English
Date published: 07/24/2017
Academic Unit: Graduate College Admin and Gen; Microbiology and Immunology; International Programs; Epidemiology; Pathology; Biostatistics; Medicine Administration; Internal Medicine
Record Identifier: 9983997365302771

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