Analysis of the Antigenic Properties of Membrane Proteins of Mycobacterium tuberculosis

• Published in: Scientific reports Vol. 9; no. 1; p. 3042
• Main Authors: Li, Haifeng, Liu, Liguo, Zhang, Wei-jia, Zhang, Xiaobing, Zheng, Jianhua, Li, Li, Zhu, Xiuyun, Yang, Qianting, Zhang, Mingxia, Liu, Haiying, Chen, Xinchun, Jin, Qi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.02.2019; Nature Publishing Group
• Subjects: 631/250/255/1856; 631/326/2521; 82/1; 82/47; 82/58; 82/80; 82/83; Adolescent; Adult; Aged; Animals; Antigens; Antigens, Bacterial - blood; Antigens, Bacterial - genetics; Antigens, Bacterial - immunology; Antigens, Bacterial - isolation & purification; Bacterial Proteins - blood; Bacterial Proteins - genetics; Bacterial Proteins - immunology; Bacterial Proteins - isolation & purification; Biomarkers; Biomarkers - blood; Cloning, Molecular; Computational Biology; Developing countries; Disease Models, Animal; Enzyme-linked immunosorbent assay; ESAT-6 antigen; Female; Humanities and Social Sciences; Humans; Immune response; Immune response (cell-mediated); Immunity, Cellular; Immunity, Humoral; Immunoglobulin G; Interferon-gamma - immunology; Interferon-gamma - metabolism; LDCs; Leukocytes (mononuclear); Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Male; Membrane proteins; Membrane Proteins - blood; Membrane Proteins - genetics; Membrane Proteins - immunology; Membrane Proteins - isolation & purification; Mice; Middle Aged; multidisciplinary; Mycobacterium tuberculosis - immunology; Peripheral blood mononuclear cells; Proteins; Recombinant Proteins - immunology; Recombinant Proteins - isolation & purification; Science; Science (multidisciplinary); Tuberculosis; Tuberculosis Vaccines - immunology; Tuberculosis Vaccines - therapeutic use; Tuberculosis, Pulmonary - blood; Tuberculosis, Pulmonary - diagnosis; Tuberculosis, Pulmonary - immunology; Tuberculosis, Pulmonary - prevention & control; Vaccines; Western blotting; Young Adult; γ-Interferon
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-39402-z

Tuberculosis (TB) is a continuing major threat to global health and a leading cause of death, particularly in developing countries. In this study, we aimed to identify a specific and sensitive diagnostic biomarker and develop a vaccine to prevent this disease. We investigated membrane proteins to reveal biomarkers in serum and peripheral blood mononuclear cells (PBMCs) obtained from TB patients. We employed Western blotting to evaluate serological immunoglobulin G levels, and Enzyme Linked Immunospot (ELISpot) to assess the antigen-specific cellular interferon-γ secretion from PBMCs after membrane protein stimulation. A total of 219 membrane proteins were identified, 52 exhibited at a higher levels than the 38-kDa prositive control. Of these 18 exhibited reacted ratios above 1, especially Rv1111c (427–981), with a ratios at 3.38. Accuracy and sensitivity were markedly higher for the top two antigen candidates, Rv0232 and Rv1115, after two rounds of ELISpot tests than ESAT-6 in the commercial kit (42.15 and 43.62%, respectively). These two proteins were administered to mice to detect whether they acted as effective antigens in vivo . These data provide a comprehensive view of the membranes involved in humoural and cellular immune responses that may be used as biomarkers for TB and candidates for a vaccine.