title: A multistage mycobacterium tuberculosis subunit vaccine LT70 including latency antigen Rv2626c induces long-term protection against tuberculosis.
abstract: To develop an effective subunit vaccine which could target tubercle bacilli with different metabolic states and provide effective protective immunity, we fused antigens ESAT6, Ag85B, peptide 190-198 of MPT64, and Mtb8.4 mainly expressed by proliferating bacteria and latency-associated antigen Rv2626c together to construct a multistage protein ESAT6-Ag85B-MPT64(190-198)-Mtb8.4-Rv2626c (LT70 for short) with the molecular weight of 70 kDa. The human T-cell responses to LT70 and other antigens were analyzed. The immune responses of LT70 in the adjuvant of DDA and Poly I:C and its protective efficacy against Mycobacterium tuberculosis (M. tuberculosis) infection in C57BL/6 mice were evaluated. The results showed that LT70 was stably produced in Escherichia coli and could be purified by successive salting-out and chromatography. LT70 could be strongly recognized by human T cells from TB patients and persons who are supposed latently infected with M. tuberculosis. The subunit vaccine LT70 generated strong antigen-specific humoral and cell-mediated immunity, and induced higher protective efficacy (5.41±0.37 Log10 CFU in lung) than traditional vaccine Bacillus Calmette-Guerin (6.01±0.33 Log10 CFU) and PBS control (6.53±0.26 Log10 CFU) at 30 weeks post vaccination (10 weeks post-challenge) against M. tuberculosis infection (p < 0.05). These findings suggested that LT70 would be a promising subunit vaccine candidate against M. tuberculosis infection.
authors.affiliation: a 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.|b Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University , Lanzhou , China.
authors.forename: Xun
authors.initials: X
authors.lastname: Liu
authors.affiliation: a 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.|b Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University , Lanzhou , China.
authors.forename: Jinxiu
authors.initials: J
authors.lastname: Peng
authors.affiliation: c Lanzhou Institute of Biological Products , Lanzhou , China.
authors.forename: Lina
authors.initials: L
authors.lastname: Hu
authors.affiliation: a 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: a 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.|b Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University , Lanzhou , China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Niu
authors.affiliation: a 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.|b Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University , Lanzhou , China.
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Bai
authors.affiliation: a 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: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: a 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.|b Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University , Lanzhou , China.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: a 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: c Lanzhou Institute of Biological Products , Lanzhou , China.
authors.forename: Bingxiang
authors.initials: B
authors.lastname: Wang
authors.affiliation: a 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: Huiyu
authors.initials: H
authors.lastname: Chen
authors.affiliation: d ABSL-3 Lab, Wuhan University , Wuhan , China.
authors.forename: Ming
authors.initials: M
authors.lastname: Guo
authors.affiliation: a 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.|b Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University , Lanzhou , China.
authors.forename: Bingdong
authors.initials: B
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008810:Mice, Inbred C57BL; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D011993:Recombinant Fusion Proteins; D032581:Tuberculosis Vaccines; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic
keywords: LT70; Rv2626c; mycobacterium tuberculosis; protective efficacy; subunit vaccine