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Antiviral innate immune activation in HIV-infected adults negatively affects H1/IC31-induced vaccine-specific memory CD4+ T cells

Lenz, Nicole and Schindler, Tobias and Kagina, Benjamin M. and Zhang, Jitao David and Lukindo, Tedson and Mpina, Maxmillian and Bang, Peter and Kromann, Ingrid and Hoff, Søren T. and Andersen, Peter and Reither, Klaus and Churchyard, Gavin J. and Certa, Ulrich and Daubenberger, Claudia A.. (2015) Antiviral innate immune activation in HIV-infected adults negatively affects H1/IC31-induced vaccine-specific memory CD4+ T cells. Clinical and vaccine immunology, Vol. 22, H. 7. pp. 688-696.

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Official URL: http://edoc.unibas.ch/dok/A6411128

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Abstract

Tuberculosis (TB) remains a global health problem, with vaccination being a necessary strategy for disease containment and elimination. A TB vaccine should be safe and immunogenic as well as efficacious in all affected populations, including HIV-infected individuals. We investigated the induction and maintenance of vaccine-induced memory CD4(+) T cells following vaccination with the subunit vaccine H1/IC31. H1/IC31 was inoculated twice on study days 0 and 56 among HIV-infected adults with CD4(+) lymphocyte counts of <350 cells/mm(3). Whole venous blood stimulation was conducted with the H1 protein, and memory CD4(+) T cells were analyzed using intracellular cytokine staining and polychromatic flow cytometry. We identified high responders, intermediate responders, and nonresponders based on detection of interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ) expressing central (TCM) and effector memory CD4(+) T cells (TEM) 182 days after the first immunization. Amplicon-based transcript quantification using next-generation sequencing was performed to identify differentially expressed genes that correlated with vaccine-induced immune responses. Genes implicated in resolution of inflammation discriminated the responders from the nonresponders 3 days after the first inoculation. The volunteers with higher expression levels of genes involved in antiviral innate immunity at baseline showed impaired H1-specific TCM and TEM maintenance 6 months after vaccination. Our study showed that in HIV-infected volunteers, expression levels of genes involved in the antiviral innate immune response affected long-term maintenance of H1/IC31 vaccine-induced cellular immunity. (The clinical trial was registered in the Pan African Clinical Trials Registry [PACTR] with the identifier PACTR201105000289276.).
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Clinical Immunology (Daubenberger)
UniBasel Contributors:Daubenberger, Claudia and Reither, Klaus
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Society for Microbiology
ISSN:1556-6811
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:04 Sep 2015 14:30
Deposited On:04 Sep 2015 14:30

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