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Nonlytic Fc-fused IL-7 synergizes with Mtb32 DNA vaccine to enhance antigen-specific T cell responses in a therapeutic model of tuberculosis

Authors
 So-Shin Ahn  ;  Bo-Young Jeon  ;  Seong-Jeong Park  ;  Dong-Hoon Choi  ;  Sun-Hwa Ku  ;  Sang-Nae Cho  ;  Young-Chul Sung 
Citation
 VACCINE, Vol.31(27) : 2884-2890, 2013 
Journal Title
VACCINE
ISSN
 0264-410X 
Issue Date
2013
MeSH
Animals ; Antigens, Bacterial/genetics ; Antigens, Bacterial/immunology* ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Drug Synergism ; Female ; Immunoglobulin Fc Fragments/genetics ; Immunoglobulin Fc Fragments/immunology* ; Interferon-gamma/biosynthesis ; Interleukin-7/genetics ; Interleukin-7/immunology* ; Membrane Proteins/genetics ; Membrane Proteins/immunology* ; Mice ; Mice, Inbred C57BL ; Mycobacterium tuberculosis/immunology ; Tuberculosis Vaccines/immunology* ; Tuberculosis, Pulmonary/immunology ; Tuberculosis, Pulmonary/prevention & control* ; Vaccination ; Vaccines, DNA/immunology*
Keywords
Tuberculosis ; IL-7-nFc ; Mtb32 ; DNA vaccine ; Adjuvant ; Immunotherapy
Abstract
Improvement to the immunogenicity of DNA vaccines was evaluated in a Mycobacterium tuberculosis (MTB) infection mouse model examining the combined effects of nonlytic Fc-fused IL-7 DNA (IL-7-nFc) and Flt3-ligand fused Mtb32 (F-Mtb32) DNA. Mice were treated with conventional chemotherapy for 6 weeks from 4 weeks after aerosol infection of MTB. Following the start of chemotherapy, DNA immunizations were administered five times with 2-week intervals. Coadministration of IL-7-nFc and F-Mtb32 DNA given during chemotherapy synergistically enhanced the magnitude of Mtb32-specific T cell responses and sustained for one-year after the last immunization assessed by IFN-γ ELISPOT assay. After dexamethasone treatment, a significantly reduced MTB reactivation was observed in mice received both IL-7-nFc and F-Mtb32 DNA, compared with F-MTb32 DNA alone or with control mice. In addition, mice treated with IL-7-nFc and F-Mtb32 DNA together showed improved lung pathology and reduced pulmonary inflammation values relative to F-Mtb32 DNA or saline injected mice. Intracellular cytokine staining revealed that the protection levels induced by combination therapy with IL-7-nFc and F-Mtb32 DNA was associated with enhanced Mtb32-specific IFN-γ secreting CD4+ T cell responses and CD8+ T cell responses stimulated with CTL epitope peptide in the lungs and spleens. These data suggest that IL-7-nFc as a novel TB adjuvant may facilitate therapeutic TB DNA vaccine to the clinics through significant enhancement of codelivered DNA vaccine-induced T cell immunity.
Full Text
http://www.sciencedirect.com/science/article/pii/S0264410X13004684
DOI
10.1016/j.vaccine.2013.04.029
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Cho, Sang Nae(조상래)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/87053
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