Allison F Christiaansen1, Upasna Gaur Dixit2, Rhea N Coler3, Anna Marie Beckmann3, Steven G Reed3, Patricia L Winokur2, M Bridget Zimmerman4, Steven M Varga5, Mary E Wilson6. 1. Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA. 2. Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA. 3. Infectious Disease Research Institute, Seattle, WA 98102, USA. 4. Department of Biostatistics, University of Iowa, Iowa City, IA 52242, USA. 5. Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA; Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, USA; Department of Pathology, University of Iowa, Iowa City, IA 52242, USA. 6. Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA; Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA; Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, USA; Department of Epidemiology, University of Iowa, Iowa City, IA 52242, USA; Veterans' Affairs Medical Center, Iowa City, IA 52242, USA. Electronic address: mary-wilson@uiowa.edu.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. Published by Elsevier Ltd.
RCT Entities:
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. Published by Elsevier Ltd.
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