DNA Vaccines Against Mycobacterium Tuberculosis And Brucella Abortus

DNA vaccination has become a favored strategy for inducing immunity. In the current work, we tried many ways to improve the design of DNA vaccines against tuberculosis and brucellosis, to elucidate the mechanisms of these vaccines, and to evaluate the therapeutic effect of DNA vaccines in combination with traditional antibiotic drugs. Combined DNA encoding Ag85B, MPT64, and MPT83 demonstrated significantly higher protection than any of the three single DNA vaccine or BCG in mice or bovine. Moreover, these results demonstrated that protective immunity against M. tuberculosis principally depended on the recruitment of antigen-specific CD4+ T cells. When C57BL/6 mice were inoculated with the combined DNA vaccine encoding BCSP31, SOD, and L7/L12, we found that both CD8+ and CD4+ T cells were critical for protection against B. abortus. In subsequent study, we combined these two trivalent DNA vaccines to test its ability to protect against two intracellular pathogens.To reinforce the efficacy of combined DNA vaccines, we added plasmids encoding cytokines such as IL-2, IL-12, and IL-15 as genetic adjuvants to magnify the TH1 type response. We observed that these immune adjuvants increased the number of M. tuberculosis or B. abortus-specific IFN-γ-producing cells and caused a significant reduction in bacterial growth compared with non-adjuvant groups. The clinically safe adjuvant KLKL5KLK was found to enhance the efficancy of CD4+T cells and CTLs and prolonged the protection duration. Combined DNA vaccines in DDA resulted in significant increases in both specific IgG and IFN-γproduction, while prime-boost strategies improved the efficacy of DNA vaccines.Reduction of the quantity of plasmid DNA required may represent one of the key factors for successful DNA vaccination. We addressed this question using a novel DNA delivery system based on cationic DL-lactide-co-glycolide (PLGA) microparticles. In vaccine/challenge experiments, mice receiving a single dose of PLGA encapsulated DNA were protected against M. tuberculosis challenge at levels comparable to groups of mice immunized with three doses of non-encapsulated DNA vaccine or with M. bovis BCG.Although most cases of tuberculosis (TB) can be cured with antibiotics, the chemotherapeutic regimens available are far from ideal for their side effects, such as protracted duration of treatment, poor patient compliance, high failure rate and drug resistance. We demonstrate that boosting the efficiency of the immune system with combined DNA vaccine may be a valuable adjunct to shorten the duration of antibacterial chemotherapy. Mice treated with combined DNA vaccine along with isoniazid and pyrazinamide showed significantly higher interferon-γresponses to a mixture of three specific antigens, which were accompanied by a significant reduction in colony-forming unit in H37Rv-infected animals 3–5 months after treatment. These results suggest that the combined DNA vaccine along with conventional TB chemotherapy has strong potential for TB immunotherapy and may provide new alternatives to control the disease.