title: Prime-boost vaccination with Bacillus Calmette Guerin and a recombinant adenovirus co-expressing CFP10, ESAT6, Ag85A and Ag85B of Mycobacterium tuberculosis induces robust antigen-specific immune responses in mice.
abstract: Tuberculosis (TB) remains to be a prevalent health issue worldwide. At present, Mycobacterium bovis Bacillus Calmette Guerin (BCG) is the singular anti-TB vaccine available for the prevention of disease in humans; however, this vaccine only provides limited protection against Mycobacterium tuberculosis (Mtb) infection. Therefore, the development of alternative vaccines and strategies for increasing the efficacy of vaccination against TB are urgently required. The present study aimed to evaluate the ability of a recombinant adenoviral vector (Ad5-CEAB) co-expressing 10-kDa culture filtrate protein, 6-kDa early-secreted antigenic target, antigen 85 (Ag85)A and Ag85B of Mtb to boost immune responses following primary vaccination with BCG in mice. The mice were first subcutaneously primed with BCG and boosted with two doses of Ad5-CEAB via an intranasal route. The immunological effects of Ad5-CEAB boosted mice primed with BCG were then evaluated using a series of immunological indexes. The results demonstrated that the prime-boost strategy induced a potent antigen-specific immune response, which was primarily characterized by an enhanced T cell response and increased production of cytokines, including interferon-γ, tumor necrosis factor-α and interleukin-2, in mice. In addition, this vaccination strategy was demonstrated to have an elevated humoral response with increased concentrations of antigen-specific bronchoalveolar lavage secretory immunoglobulin (Ig)A and serum IgG in mice compared with those primed with BCG alone. These data suggested that the regimen of subcutaneous BCG prime and mucosal Ad5-CEAB boost was a novel strategy for inducing a broad range of antigen-specific immune responses to Mtb antigens in vivo, which may provide a promising strategy for further development of adenoviral-based vaccine against Mtb infection.
authors.affiliation: Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in Western China, College of Life Science, Ningxia University, Ningxia 750021, P.R. China.
authors.forename: Wu
authors.initials: W
authors.lastname: Li
authors.affiliation: Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in Western China, College of Life Science, Ningxia University, Ningxia 750021, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in Western China, College of Life Science, Ningxia University, Ningxia 750021, P.R. China.
authors.forename: Guangcun
authors.initials: G
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, P.R. China.
authors.forename: Liping
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in Western China, College of Life Science, Ningxia University, Ningxia 750021, P.R. China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Liu
authors.affiliation: Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in Western China, College of Life Science, Ningxia University, Ningxia 750021, P.R. China.
authors.forename: Yujiong
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000276:immunology; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D001500:BCG Vaccine / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics* / Q000276:immunology; D016207:Cytokines / Q000032:analysis; D005260:Female; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D056724:Immunity, Humoral; D007117:Immunization, Secondary; D007070:Immunoglobulin A / Q000032:analysis / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000032:analysis; D051379:Mice; D008813:Mice, Inbred ICR; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology* / Q000473:pathology / Q000662:veterinary; D032581:Tuberculosis Vaccines
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; D016207:Cytokines; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D032581:Tuberculosis Vaccines; D007371:Interferon-gamma; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis; C121433:antigen 85B, Mycobacterium tuberculosis