title: Novel vaccine potential of Rv3131, a DosR regulon-encoded putative nitroreductase, against hyper-virulent Mycobacterium tuberculosis strain K.
abstract: Accumulating evidence indicates that latency-associated Mycobacterium tuberculosis (Mtb)-specific antigens from the dormancy survival regulator regulon (DosR) may be promising novel vaccine target antigens for the development of an improved tuberculosis vaccine. After transcriptional profiling of DosR-related genes in the hyper-virulent Beijing Mtb strain K and the reference Mtb strain H37Rv, we selected Rv3131, a hypothetical nitroreductase, as a vaccine antigen and evaluated its vaccine efficacy against Mtb K. Mtb K exhibited stable and constitutive up-regulation of rv3131 relative to Mtb H37Rv under three different growth conditions (at least 2-fold induction) including exponential growth in normal culture conditions, hypoxia, and inside macrophages. Mice immunised with Rv3131 formulated in GLA-SE, a well-defined TLR4 adjuvant, displayed enhanced Rv3131-specific IFN-γ and serum IgG2c responses along with effector/memory T cell expansion and remarkable generation of Rv3131-specific multifunctional CD4+T cells co-producing TNF-α, IFN-γ and IL-2 in both spleen and lung. Following challenge with Mtb K, the Rv3131/GLA-SE-immunised group exhibited a significant reduction in bacterial number and less extensive lung inflammation accompanied by the obvious persistence of Rv3131-specific multifunctional CD4+T cells. These results suggest that Rv3131 could be an excellent candidate for potential use in a multi-antigenic Mtb subunit vaccine, especially against Mtb Beijing strains.
authors.affiliation: Department of Microbiology, Yonsei University College of Medicine, Seoul 03722, South Korea.|Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, South Korea.
authors.forename: Kee Woong
authors.initials: KW
authors.lastname: Kwon
authors.affiliation: Department of Microbiology, Yonsei University College of Medicine, Seoul 03722, South Korea.|Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, South Korea.
authors.forename: Woo Sik
authors.initials: WS
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Yonsei University College of Medicine, Seoul 03722, South Korea.|Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, South Korea.
authors.forename: Hongmin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Yonsei University College of Medicine, Seoul 03722, South Korea.|Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, South Korea.
authors.forename: Seung Jung
authors.initials: SJ
authors.lastname: Han
authors.affiliation: Department of Microbiology, Yonsei University College of Medicine, Seoul 03722, South Korea.
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Hahn
authors.affiliation: Department of Microbiology Research, International Tuberculosis Research Center, Changwon 51755, South Korea.
authors.forename: Jong Seok
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, South Korea.
authors.forename: Ki Taek
authors.initials: KT
authors.lastname: Nam
authors.affiliation: Department of Microbiology, Yonsei University College of Medicine, Seoul 03722, South Korea.|Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, South Korea.
authors.forename: Sang-Nae
authors.initials: SN
authors.lastname: Cho
authors.affiliation: Department of Microbiology, Yonsei University College of Medicine, Seoul 03722, South Korea.|Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, South Korea.
authors.forename: Sung Jae
authors.initials: SJ
authors.lastname: Shin
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D007114:Immunization; D051379:Mice; D009601:Nitroreductases / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D011494:Protein Kinases / Q000235:genetics / Q000276:immunology; D032581:Tuberculosis Vaccines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; D016207:Cytokines; D004268:DNA-Binding Proteins; C542863:DosR protein, Mycobacterium tuberculosis; D032581:Tuberculosis Vaccines; D009601:Nitroreductases; D011494:Protein Kinases