Application of DNA vaccine in treatment of mice with multi-drug resistant tuberculosis

Abstract

Objective To establish foundation for new strategy and program on immune therapy of multi-drug resistant tuberculosis (MDR-TB) by studying the therapeutic effects of Mycobacterium tuberculosis Ag85A plasmid DNA vaccine alone or combined with drugs on MDR-TB mice. Methods Sixty 6-8 weeks old female BALB/C mice were injected via tail vein with clinical isolate Mycobacterium tuberculosis HB361 which was highly resistant to rifampin (RFP) and lowly resistant to isoniazid. The mice were randomly divided into six groups, ten mice in each group. From the second day after infection,the mice respectively received pVAX1 vector (group A), RFP (group B), pyrazinamide (PZA) (group C),Ag85A plasmid DNA vaccine (group D), Ag85A plasmid DNA vaccine combined with RFP (group E),Ag85A plasmid DNA vaccine combined with PZA (group F) for sixty days. Four weeks after the end of treatment,the lung, liver and spleen of the mice were taken and their pathological changes, weight and colony count were examined. Results Four weeks after infection, the numbers of bacteria in lung and spleen of the mice reached up to 1.5×107 CFU and 1.1 × 106 CFU,respectively. The death rates of mice in group A and group B were both 10% ,and the mice in other groups were alive. Four weeks after the end of treatment,lung pathology in the treated groups showed that the lung lesions were slight and limited,normal alveolar structure were seen, and the profile of the alveoli was relatively clear. Compared with group A, group C, D, E, F reduced by 1.18,1.35,1.38,1.08 logs on the colony count of lung, and reduced by 0.91,1.00,1.26 and 1.03 logs on the colony count of spleen (P＜0.01), respectively. Conclusions Mycobacterium tuberculosis Ag85A plasmid DNA vaccine alone or combined with drugs has significant therapeutic effects on MDR-TB mice. Ag85A plasmid DNA vaccine combined with anti-tuberculosis drugs is the most promising immunization strategy for treatment of MDR-TB. Key words: Mycobacterium tuberculosis; DNA vaccine; Multi-drug resistant tuberculosis