Co-administration and Evaluation of Immune Responses of Three DNA Vaccines Encoding Immunogenic Antigens from <i>Mycobacterium tuberculosis</i>

Abstract

Background: Ineffectiveness of BCG vaccine in controlling tuberculosis (TB) and co-infection of TB and HIV have turned TB into a serious global threat. Therefore, the development of an alternative vaccine to BCG and/or antimycobacterial drugs is an urgent need. Here, three chimeric DNA constructs consisting of Mtb32C-HBHA, Ag85a-Tb10.4, and Ag85a-cfp10 made in our previous studies were co-administered to BALB/c mice to evaluate their immune responses using a prime-boost regimen in which the animals were first immunized with BCG and then administered with DNA vaccines. Methods: In order to evaluate the immunogenicity of three DNA constructs, the levels of several immunomodulatory cytokines were measured in vaccinated mice. Thirty female BALB/c mice were divided into the following groups (n = 10): control (receiving pcDNA 3.1+ intramuscularly), vaccine (receiving recombinant vectors intramuscularly), and vaccine-BCG (receiving BCG subcutaneously followed by recombinant vectors intramuscularly). Results: The levels of IL-4, IL-12, TGF-β, IFN-γ, and IL-10 were higher in the immunized groups than in the control group (P < 0.05). Besides, the levels of IL-12 and IFN-γ were much higher in the BCG-vaccine group than in the vaccine alone group. In the case of IFN-γ, a significant difference was observed between the vaccine and BCG-vaccine groups at P < 0.001 while in the case of IL-12, the difference was significant at P < 0.05. However, in the case of IL-10, IL-4, and TGF-β, the differences between the vaccine and BCG-vaccine groups were not significant (P > 0.05). Conclusions: Our results proved that using a chimeric DNA vaccine as a booster in the prime-boost strategy could significantly enhance the efficacy of BCG. This study suggests that the use of such DNA vaccines encoding mycobacterial immunogenic antigens as boosters enhances the efficacy of BCG.