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Co-Administration and Evaluation of Immune Responses of Three Dna Vaccines Encoding Immunogenic Antigens From Mycobacterium Tuberculosis Publisher



Peeridogaheh H1 ; Teimourpour R1 ; Habibzadeh S2 ; Mohammadshahi J2 ; Gholoobi A3 ; Teimourpour A4 ; Meshkat Z5
Authors
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Authors Affiliations
  1. 1. Department of Microbiology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
  2. 2. Departments of Infectious Diseases, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
  3. 3. Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
  4. 4. Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Source: Archives of Clinical Infectious Diseases Published:2019


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 BCGvaccine 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. © 2019, Archives of Clinical Infectious Diseases.