title: Protective and therapeutic efficacy of Mycobacterium smegmatis expressing HBHA-hIL12 fusion protein against Mycobacterium tuberculosis in mice.
abstract: Tuberculosis (TB) remains a major worldwide health problem. The only vaccine against TB, Mycobacterium bovis Bacille Calmette-Guerin (BCG), has demonstrated relatively low efficacy and does not provide satisfactory protection against the disease. More efficient vaccines and improved therapies are urgently needed to decrease the worldwide spread and burden of TB, and use of a viable, metabolizing mycobacteria vaccine may be a promising strategy against the disease. Here, we constructed a recombinant Mycobacterium smegmatis (rMS) strain expressing a fusion protein of heparin-binding hemagglutinin (HBHA) and human interleukin 12 (hIL-12). Immune responses induced by the rMS in mice and protection against Mycobacterium tuberculosis (MTB) were investigated. Administration of this novel rMS enhanced Th1-type cellular responses (IFN-γ and IL-2) in mice and reduced bacterial burden in lungs as well as that achieved by BCG vaccination. Meanwhile, the bacteria load in M. tuberculosis infected mice treated with the rMS vaccine also was significantly reduced. In conclusion, the rMS strain expressing the HBHA and human IL-12 fusion protein enhanced immunogencity by improving the Th1-type response against TB, and the protective effect was equivalent to that of the conventional BCG vaccine in mice. Furthermore, it could decrease bacterial load and alleviate histopathological damage in lungs of M. tuberculosis infected mice.
authors.affiliation: Division of Infection and Immunology, Laboratory Animals Center, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
authors.forename: Shanmin
authors.initials: S
authors.lastname: Zhao
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
authors.forename: Fengfeng
authors.initials: F
authors.lastname: Mao
authors.forename: Caiqin
authors.initials: C
authors.lastname: Zhang
authors.forename: Bing
authors.initials: B
authors.lastname: Bai
authors.forename: Hai
authors.initials: H
authors.lastname: Zhang
authors.forename: Changhong
authors.initials: C
authors.lastname: Shi
authors.forename: Zhikai
authors.initials: Z
authors.lastname: Xu
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D015153:Blotting, Western; D003001:Cloning, Molecular; D058501:Enzyme-Linked Immunospot Assay; D005455:Fluorescent Antibody Technique; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000494:pharmacology / Q000627:therapeutic use*; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008565:Membrane Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D020102:Mycobacterium smegmatis / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000276:immunology; D010641:Phenotype; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D011995:Recombination, Genetic / Q000187:drug effects; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome; D014376:Tuberculosis / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C440647:HbhA protein, Mycobacterium tuberculosis; D008565:Membrane Proteins; D020011:Protective Agents; D011993:Recombinant Fusion Proteins; D032581:Tuberculosis Vaccines; D018664:Interleukin-12; D007371:Interferon-gamma