title: T-bet acts as a powerful adjuvant in Ag85B DNA‑based vaccination against             tuberculosis.
abstract: Owing to the limitations of traditional Bacillus Calmette-Guerin vaccines and the low efficacy of DNA vaccines expressing single antigens of Mycobacterium tuberculosis, there is a pressing requirement for adjuvants capable of strengthing the immunogenicity and effectiveness of these vaccines against tuberculosis (TB). T-bet (TBX21) is a transcription factor, which controls the optimal development of type-1 immune responses responsible for the potent protection of vaccines against TB. However, little is known about the efficiency of the TB vaccine combined with T-bet. In this study, we report an approach to intensify the immunogenicity of Ag85B DNA-based vaccines using T-bet as an adjuvant. Balb/c mice were immunized by 3 intramuscular inoculations with pcDNA3.1-FLAG-T-bet in combination with pcDNA3.1-FLAG-Ag85B, and the immune responses were compared with those induced by vaccination with Ag85B DNA alone. We found that pcDNA3.1-T-bet-Ag85B not only induced evidently higher IgG2a antibody responses, but also increased the production of interferon-γ (IFN-γ) and interleukin (IL)-2 with the concomitant repression of IL-4 and IL-10 compared with pcDNA3.1-Ag85B alone or the empty vector. Thus, plasmid DNA coding for T-bet enhanced Ag85B-specific immune responses and shifted them to a predominant Th1-type immune response. In conclusion, T-bet is an efficacious Th1-inducing adjuvant in the context of the Ag85B DNA-based vaccination, and could also prove to be a promising candidate for DNA vaccine development against TB.
authors.affiliation: Department of Medical Immunology, Medical School and Institute of Infection and Immunity, Anhui University of Science and Technology, Huainan, Anhui 232001, PR China.
authors.forename: Dong
authors.initials: D
authors.lastname: Hu
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Rongbo
authors.initials: R
authors.lastname: Zhang
authors.forename: Liping
authors.initials: L
authors.lastname: Chen
mesh_terms: D000217:Acyltransferases / Q000235:genetics* / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000235:genetics*; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000918:Antibody Specificity; D000942:Antigens, Bacterial / Q000235:genetics* / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics* / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D008168:Lung / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000235:genetics; D013154:Spleen / Q000276:immunology / Q000382:microbiology; D020825:T-Box Domain Proteins / Q000235:genetics*; D014376:Tuberculosis / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology*; D000098815:T-bet Transcription Factor
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis