Yan Liang, Xiaoyan Zhang, Li Xiao, Xuejuan Bai, Xiaomei Wang, Yourong Yang, Junxian Zhang, Jinying Song, Yinping Liu, Ning Li and Xueqiong Wu Pages 249 - 255 ( 7 )
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-γ (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 log10 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.
DNA vaccine, pVAX1-rv1419 DNA, Immunotherapy, Mycobacterium tuberculosis, Rv1419 protein, Immunization.
Army Tuberculosis Prevention and Control Key Laboratory, Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Institute of Tuberculosis Research, the 309th Hospital of Chinese PLA, Beijing 100091, China.