Immunogenicity and Therapeutic Effects of pVAX-rv1419 DNA from Mycobacterium tuberculosis

Background: Tuberculosis (TB) is threatening disease in China and new therapeutic agents and regimens to treat TB are urgently needed. Objective: In this study, a DNA vaccine expressing Mycobacterium tuberculosis (MTB) Rv1419 antigen was constructed and its immunogenicity and therapeutic effects were evaluated. Method: Normal mice and TB model mice were immunized intramuscularly three times at two-week intervals with saline, plasmid vector pVAX1, M vaccae vaccine, pVAX1- ag85a (rv3804c) DNA or pVAX1-rv1419 DNA, respectively. Results: At three weeks after the last immunization, flow cytometry showed a higher proportion of CD4(+) T cells expressing IFN-gamma (Th1) in response to Rv1419 protein in blood from the pVAX1- rv1419 DNA group compared with the saline and vector groups (P<0.05), suggesting a predominant Th1 immune response. Live bacterial loads in lungs and spleens were lower by 0.41 log(10) in the pVAX1-rv1419 DNA group than in the saline controls. In addition, pathological changes in the lungs of the DNA vaccinated groups were less. These results suggest that pVAX1- rv1419 DNA could be effective for the treatment of TB, significantly increasing the Th1-type cellular immune response, and inhibiting the growth of MTB. Conclusion: Therefore pVAX1- rv1419 DNA is a candidate for inclusion in a therapeutic combination DNA vaccine against TB.