title: Adenylate kinase: a novel antigen for immunodiagnosis and subunit vaccine against tuberculosis.
abstract: Mycobacterium tuberculosis (M.tb)-derived antigens capable of inducing strong cellular and/or humoral responses are potential targets for both immunodiagnosis and vaccine development against tuberculosis (TB). In the present study, we identified adenylate kinase (ADK, Rv0733) as an antigen that induces high cellular and antibody responses in active TB patients. We consequently tested the use of ADK-specific T cells and antibodies as biomarkers for TB diagnosis. The ADK-specific IFN-γ-producing cells detected by ELISPOT assay showed a sensitivity of 85.0 % and specificity of 94.15 % for TB diagnosis while ADK-specific IgG antibody showed a sensitivity of 40.35 % and specificity of 96.43 %. Combining ADK-specific cellular and antibody responses increased the sensitivity to 91.59 % and the specificity to 96.15 %. Immunogenicity and protection against M.tb infection were further tested in a murine model. Immunization with ADK protein elicited strong specific T- and B-cell responses, and provided protection against the virulent H37Rv stain of M.tb resulting in lower bacilli load in the spleens and lungs. More ADK-specific polyfunctional Th1 cells were observed in the lungs when compared to adjuvant-immunized mice. ADK thus may serve as a novel M.tb antigen for TB immunodiagnosis and development of subunit vaccines.
  
  
  
  ADK induces strong immune responses both in humans and mice. ADK-specific IFN-γ production and B-cell responses have high potential for TB diagnosis. ADK immunization provides protection against M.tb infection.
authors.affiliation: Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, Shanghai, 200025, China.|Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, 100045, China.
authors.forename: Yangjiong
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Shanghai Key Laboratory of Tuberculosis, Diagnosis and Treat Centre of Tuberculosis, Shanghai Pulmonary Hospital Affiliated to Tongji University School of Medicine, Shanghai, 200433, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sha
authors.affiliation: Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, Shanghai, 200025, China.
authors.forename: Zhaofeng
authors.initials: Z
authors.lastname: Tian
authors.affiliation: Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, Shanghai, 200025, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, Shanghai, 200025, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Ji
authors.affiliation: Shanghai Key Laboratory of Tuberculosis, Diagnosis and Treat Centre of Tuberculosis, Shanghai Pulmonary Hospital Affiliated to Tongji University School of Medicine, Shanghai, 200433, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, Shanghai, 200025, China.
authors.forename: Huiyu
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, Shanghai, 200025, China.
authors.forename: Shujun
authors.initials: S
authors.lastname: Wang
authors.affiliation: Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, 100045, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai, 201508, China.
authors.forename: Han-Li
authors.initials: HL
authors.lastname: Wen
authors.affiliation: Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai, 201508, China.
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Zhao
authors.affiliation: Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, 100045, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lu
authors.affiliation: Shanghai Key Laboratory of Tuberculosis, Diagnosis and Treat Centre of Tuberculosis, Shanghai Pulmonary Hospital Affiliated to Tongji University School of Medicine, Shanghai, 200433, China.
authors.forename: Heping
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai, 201508, China. xyfan008@fudan.edu.cn.
authors.forename: Xiao-Yong
authors.initials: XY
authors.lastname: Fan
authors.affiliation: Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, Shanghai, 200025, China. hshen@mail.med.upenn.edu.|Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, 100045, China. hshen@mail.med.upenn.edu.|Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. hshen@mail.med.upenn.edu.
authors.forename: Hao
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, Shanghai, 200025, China. ywang@sibs.ac.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000263:Adenylate Kinase / Q000008:administration & dosage* / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000008:administration & dosage* / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D001426:Bacterial Proteins / Q000008:administration & dosage* / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D056724:Immunity, Humoral / Q000187:drug effects; D000071497:Immunogenicity, Vaccine; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D032581:Tuberculosis Vaccines / Q000008:administration & dosage*; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D022223:Vaccines, Subunit
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D032581:Tuberculosis Vaccines; D022223:Vaccines, Subunit; D007371:Interferon-gamma; D000263:Adenylate Kinase
keywords: Adenylate kinase; Antigenicity and immunogenicity; Immunodiagnosis; Subunit vaccine; Tuberculosis