title: Recombinant BCG prime and PPE protein boost provides potent protection against acute Mycobacterium tuberculosis infection in mice.
abstract: Since BCG, the only vaccine widely used against tuberculosis (TB) in the world, provides varied protective efficacy and may not be effective for inducing long-term cellular immunity, it is in an urgent need to develop more effective vaccines and more potent immune strategies against TB. Prime-boost is proven to be a good strategy by inducing long-term protection. In this study, we tested the protective effect against Mycobacterium tuberculosis (Mtb) challenge of prime-boost strategy by recombinant BCG (rBCG) expressing PPE protein Rv3425 fused with Ag85B and Rv3425. Results showed that the prime-boost strategy could significantly increase the protective efficiency against Mtb infection, characterized by reduction of bacterial load in lung and spleen, attenuation of tuberculosis lesions in lung tissues. Importantly, we found that Rv3425 boost, superior to Ag85B boost, provided better protection against Mtb infection. Further research proved that rBCG prime-Rv3425 boost could obviously increase the expansion of lymphocytes, significantly induce IL-2 production by lymphocytes upon PPD stimulation, and inhibit IL-6 production at an early stage. It implied that rBCG prime-Rv3425 boost opted to induce Th1 immune response and provided a long-term protection against TB. These results implicated that rBCG prime-Rv3425 boost is a potent and promising strategy to prevent acute Mtb infection.
authors.affiliation: Unit of Anti-tuberculosis Immunity, Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Enzhuo
authors.initials: E
authors.lastname: Yang
authors.affiliation: Clinic and Research Center of Tuberculosis, Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Medical Microbiology and Parasitology, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: wangfeifei@fudan.edu.cn.
authors.forename: Feifei
authors.initials: F
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Honghai
authors.initials: H
authors.lastname: Wang
authors.affiliation: Unit of Anti-tuberculosis Immunity, Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: hbshen@ips.ac.cn.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Microbiology and Immunology, Center for Primate Biomedical Research, University of Illinois College of Medicine, 835 S. Wolcott Avenue, MC790, Chicago 60612, IL, United States.
authors.forename: Zheng W
authors.initials: ZW
authors.lastname: Chen
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D001500:BCG Vaccine / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D007117:Immunization, Secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*
chemical_list: D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; C582018:PPE2 protein, Mycobacterium tuberculosis; D011993:Recombinant Fusion Proteins
keywords: Ag85B; Prime-boost strategy; Rv3425; Tuberculosis