Efficient tuberculosis treatment in mice using chemotherapy and immunotherapy with the combined DNA vaccine encoding Ag85B, MPT-64 and MPT-83.
Although most cases of tuberculosis (TB) can be cured with antibiotics, relapse is common if patients do not continue chemotherapy for at least 6 months. Thus, improved therapeutic strategies are urgently needed. We previously found that the combined DNA vaccine encoding the Mycobacterium tuberculosis proteins Ag85B, MPT-64 and MPT-83 protected mice from TB following H37Rv challenge and considered whether this combined DNA vaccine has a therapeutic effect. In the present work, we demonstrate that boosting the efficiency of the immune system with the combined DNA vaccine may be a valuable adjunct to shorten the duration of antibacterial chemotherapy. Mice treated with the combined DNA vaccine along with isoniazid and pyrazinamide showed significantly higher interferon-gamma responses to a mixture of the three specific antigens (P<0.001), which were accompanied by a significant reduction in colony-forming unit in H37Rv-infected animals 3-5 months after treatment (P<0.001). These results suggest that the combined DNA vaccine along with conventional TB chemotherapy has strong potential for TB immunotherapy and may provide new alternatives to control the disease.
Yu
D-H
DH
The National Laboratory of Protein Engineering and Plant Genetic Engineering, Peking University, Beijing, China.
Hu
X-D
XD
Cai
H
H
D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics; D000995:Antitubercular Agents / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000235:genetics; D003114:Colony-Forming Units Assay; D003131:Combined Modality Therapy; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D016233:Immunotherapy, Active / Q000379:methods*; D007371:Interferon-gamma / Q000032:analysis; D018664:Interleukin-12 / Q000032:analysis; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009169:Mycobacterium tuberculosis; D009569:Nitric Oxide / Q000032:analysis; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000235:genetics*; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control*; D019444:Vaccines, DNA / Q000008:administration & dosage*
D000942:Antigens, Bacterial; D000995:Antitubercular Agents; D001426:Bacterial Proteins; C080865:MPB64 protein, Mycobacterium; C094904:MPB83 protein, Mycobacterium; D008565:Membrane Proteins; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; C065036:antigen 85, Mycobacterium bovis; D018664:Interleukin-12; D009569:Nitric Oxide; D007371:Interferon-gamma