title: Multi-Stage Tuberculosis Subunit Vaccine Candidate LT69 Provides High Protection against Mycobacterium tuberculosis Infection in Mice.
abstract: Effective tuberculosis (TB) vaccine should target tubercle bacilli with various metabolic states and confer long-term protective immunity. In this study, we constructed a novel multi-stage TB subunit vaccine based on fusion protein ESAT6-Ag85B-MPT64(190-198)-Mtb8.4-HspX (LT69 for short) which combined early expressed antigens and latency-associated antigen. The fusion protein was mixed with an adjuvant being composed of N, N'-dimethyl-N, N'-dioctadecylammonium bromide (DDA) and polyriboinosinic polyribocytidylic acid (PolyI:C) to construct subunit vaccine, whose immunogenicity and protective ability were evaluated in C57BL/6 mice. The results showed that LT69 had strong immunogenicity and high protective effect against Mycobacterium tuberculosis (M. tuberculosis) H37Rv aerosol challenge. Low-dose (2 μg) of LT69 generated long-term immune memory responses and provided effective protection, which was even higher than traditional vaccine BCG did at 30 weeks post the last vaccination. In conclusion, multistage subunit vaccine LT69 showed high and long-term protection against M. tuberculosis infection in mice, whose effect could be enhanced by using a relative low dosage of antigen.
authors.affiliation: Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation & Lanzhou Center for Tuberculosis Research, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China; Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Niu
authors.affiliation: Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation & Lanzhou Center for Tuberculosis Research, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China; Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
authors.forename: Jinxiu
authors.initials: J
authors.lastname: Peng
authors.affiliation: Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation & Lanzhou Center for Tuberculosis Research, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China; Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Bai
authors.affiliation: Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation & Lanzhou Center for Tuberculosis Research, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China; Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Liu
authors.affiliation: Lanzhou Institute of Biological Products, Lanzhou, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Hu
authors.affiliation: Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation & Lanzhou Center for Tuberculosis Research, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Lanzhou Institute of Biological Products, Lanzhou, China.
authors.forename: Bingxiang
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University，Baltimore, Maryland, United States of America.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Jianzhu
authors.initials: J
authors.lastname: Chen
authors.affiliation: Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation & Lanzhou Center for Tuberculosis Research, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Yu
authors.affiliation: ABSL-3 Lab, Wuhan University, Wuhan, China.
authors.forename: Qiaoyang
authors.initials: Q
authors.lastname: Xian
authors.affiliation: Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation & Lanzhou Center for Tuberculosis Research, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China; Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
authors.forename: Bingdong
authors.initials: B
authors.lastname: Zhu
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000276:immunology; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; C118127:HspX protein, Mycobacterium tuberculosis; C080865:MPB64 protein, Mycobacterium; C114074:Mtb8.4 protein, Mycobacterium tuberculosis; D032581:Tuberculosis Vaccines; D014614:Vaccines, Synthetic; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis