title: Enhancement of antimycobacterial Th1-cell responses by a Mycobacterium bovis BCG prime-protein boost vaccination strategy.
abstract: Tuberculosis is a major global health problem, and the only available vaccine Bacille Calmette-Guérin (BCG) is not sufficiently effective against the disease. It is extremely urgent to develop novel vaccine approaches. Previous research demonstrated that there were several Regions of Difference (RD1-16) between the substrains of BCG and Mycobacterium tuberculosis or Mycobacterium bovis. The ORFs Rv1769 and Rv1772 are located in the RD14 deletions and have not been major targets of study. However, some studies have demonstrated that the two genes (Rv1769 and Rv1772) are excellent T cell antigens, which might induce an immune response. What kind of role these ORFs might play in anti-mycobacterial immunity, however, is still unknown. In our research we used the BCG prime-protein boost strategy to immunize BALB/c mice and evaluated its immunogenicity. Our data suggest that our novel BCG-P+PRO69 vaccine could elicit the most long-lasting and strongest Th1 type cellular immune responses. This response is characterized by a strong antibody response, the proliferation rate of splenocytes, a high percentage of CD4+ and CD8+ T cells and high levels of IFN-γ in antigen-stimulated splenocyte cultures. These results indicate that prime-boost is a potent strategy and the protein of gene Rv1769 is a potential antigen or subunit vaccine to TB for further study.
authors.affiliation: Laboratory of Infection and Immunity, School of Basic Medical Science, West China Center of Medical Sciences, Sichuan University, Chengdu, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Lu
authors.forename: Zhi Yang
authors.initials: ZY
authors.lastname: Xia
authors.forename: Lang
authors.initials: L
authors.lastname: Bao
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D001500:BCG Vaccine / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D007117:Immunization, Secondary; D007371:Interferon-gamma; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000235:genetics / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology; D016366:Open Reading Frames / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000166:cytology; D018417:Th1 Cells / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology* / Q000517:prevention & control; D014611:Vaccination
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001500:BCG Vaccine; D016207:Cytokines; D007371:Interferon-gamma
keywords: BCC-C; BCG; BCG-C+P69, BCG-C+PRO69; BCG-C+P72, BCG-C+PRO72; BCG-C+PP, BCG-C+PRO-PET; BCG-P; BCG-P+P69, BCG-P+PRO69; BCG-P+P72, BCG-P+PRO72; BCG-P+PP, BCG-P+PRO-PET; Bacille Calmette-Guérin; Delayed type hypersensitivity; Immunogenicity; Pathogen microorganism; the group immunized BCG- Pasteur1173 prime protein PET32 (a+) plasmid boost; the group immunized BCG- Pasteur1173 prime protein Rv1769 boost; the group immunized BCG- Pasteur1173 prime protein Rv1772 boost; the group immunized BCG-China prime protein PET32 (a+) plasmid boost; the group immunized BCG-China prime protein Rv1769 boost; the group immunized BCG-China prime protein Rv1772 boost; the group immunized with vaccine BCG-China sub strain; the group immunized with vaccine BCG-Pasteur1173 sub strain