title: Nonlytic Fc-fused IL-7 synergizes with Mtb32 DNA vaccine to enhance antigen-specific T cell responses in a therapeutic model of tuberculosis.
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.
authors.affiliation: Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea.
authors.forename: So-Shin
authors.initials: SS
authors.lastname: Ahn
authors.forename: Bo-Young
authors.initials: BY
authors.lastname: Jeon
authors.forename: Seong-Jeong
authors.initials: SJ
authors.lastname: Park
authors.forename: Dong-Hoon
authors.initials: DH
authors.lastname: Choi
authors.forename: Sun-Hwa
authors.initials: SH
authors.lastname: Ku
authors.forename: Sang-Nae
authors.initials: SN
authors.lastname: Cho
authors.forename: Young-Chul
authors.initials: YC
authors.lastname: Sung
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004357:Drug Synergism; D005260:Female; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D015851:Interleukin-7 / Q000235:genetics / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology; D032581:Tuberculosis Vaccines / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000517:prevention & control*; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D007141:Immunoglobulin Fc Fragments; D015851:Interleukin-7; D008565:Membrane Proteins; C573996:Mtb32 antigen, Mycobacterium tuberculosis; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; C084881:flt3 ligand protein; D007371:Interferon-gamma