Antiviral Innate Immune Activation in HIV-Infected Adults Negatively Affects H1/IC31-Induced Vaccine-Specific Memory CD4+ T Cells.
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.).
Swiss Tropical and Public Health Institute, Basel, Switzerland University of Basel, Basel, Switzerland.
Nicole
http://orcid.org/0000-0001-9397-6165
N
Lenz
Swiss Tropical and Public Health Institute, Basel, Switzerland University of Basel, Basel, Switzerland Roche Pharmaceutical Research and Early Development, Department of Pharmaceutical Sciences/Translational Technologies and Bioinformatics, Roche Innovation Center Basel, Basel, Switzerland.
Tobias
T
Schindler
South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease and Molecular Medicine (IDM) and School of Child and Adolescent Health, University of Cape Town, South Africa Vaccines for Africa Initiative, Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, South Africa.
Benjamin M
BM
Kagina
Roche Pharmaceutical Research and Early Development, Department of Pharmaceutical Sciences/Translational Technologies and Bioinformatics, Roche Innovation Center Basel, Basel, Switzerland.
Jitao David
JD
Zhang
Vaccines for Africa Initiative, Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, South Africa.
Tedson
T
Lukindo
Swiss Tropical and Public Health Institute, Basel, Switzerland University of Basel, Basel, Switzerland Bagamoyo Research and Training Centre, Ifakara Health Institute, Bagamoyo, United Republic of Tanzania.
Maxmillian
M
Mpina
Statens Serum Institute, Copenhagen, Denmark.
Peter
P
Bang
Statens Serum Institute, Copenhagen, Denmark.
Ingrid
I
Kromann
Statens Serum Institute, Copenhagen, Denmark.
Søren T
ST
Hoff
Statens Serum Institute, Copenhagen, Denmark.
Peter
P
Andersen
Swiss Tropical and Public Health Institute, Basel, Switzerland University of Basel, Basel, Switzerland Bagamoyo Research and Training Centre, Ifakara Health Institute, Bagamoyo, United Republic of Tanzania.
Klaus
K
Reither
Aurum Institute, Johannesburg, South Africa London School of Hygiene and Tropical Medicine, London, United Kingdom School of Public Health, University of Witwatersrand, Johannesburg, South Africa.
Gavin J
GJ
Churchyard
Roche Pharmaceutical Research and Early Development, Department of Pharmaceutical Sciences/Translational Technologies and Bioinformatics, Roche Innovation Center Basel, Basel, Switzerland.
Ulrich
U
Certa
Swiss Tropical and Public Health Institute, Basel, Switzerland University of Basel, Basel, Switzerland claudia.daubenberger@unibas.ch.
Claudia A
CA
Daubenberger
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007113:Immunity, Innate; D007156:Immunologic Memory; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
D016207:Cytokines; D032581:Tuberculosis Vaccines; D022223:Vaccines, Subunit