Immunotherapeutic Effects of Different Doses of Mycobacterium tuberculosis ag85a/b DNA Vaccine Delivered by Electroporation

BackgroundTuberculosis (TB) is a major global public health problem. New treatment methods on TB are urgently demanded. MethodsNinety-six female BALB/c mice were challenged with 2x10(4) colony-forming units (CFUs) of MTB H(37)Rv through tail vein injection, then was treated with 10 mu g, 50 mu g, 100 mu g, and 200 mu g of Mycobacterium tuberculosis (MTB) ag85a/b chimeric DNA vaccine delivered by intramuscular injection (IM) and electroporation (EP), respectively. The immunotherapeutic effects were evaluated immunologically, bacteriologically, and pathologically. ResultsCompared with the phosphate-buffered saline (PBS) group, the CD4(+)IFN-gamma(+) T cells% in whole blood from 200 mu g DNA IM group and four DNA EP groups increased significantly (P<0.05), CD8(+)IFN-gamma(+) T cells% (in 200 mu g DNA EP group), CD4(+)IL-4(+) T cells% (50 mu g DNA IM group) and CD8(+)IL-4(+) T cells% (50 mu g and 100 mu g DNA IM group, 100 mu g and 200 mu g DNA EP group) increased significantly only in a few DNA groups (P< 0.05). The CD4(+)CD25(+) Treg cells% decreased significantly in all DNA vaccine groups (P<0.01). Except for the 10 mu g DNA IM group, the lung and spleen colony-forming units (CFUs) of the other seven DNA immunization groups decreased significantly (P<0.001, P<0.01), especially the 100 mu g DNA IM group and 50 mu g DNA EP group significantly reduced the pulmonary bacterial loads and lung lesions than the other DNA groups. ConclusionsAn MTB ag85a/b chimeric DNA vaccine could induce Th1-type cellular immune reactions. DNA immunization by EP could improve the immunogenicity of the low-dose DNA vaccine, reduce DNA dose, and produce good immunotherapeutic effects on the mouse TB model, to provide the basis for the future human clinical trial of MTB ag85a/b chimeric DNA vaccine.

Automated summary

This study demonstrates that the MTB ag85a/b chimeric DNA vaccine can induce a Th1-type cellular immune response, and DNA immunization by EP can enhance the immunogenicity of the DNA vaccine, reduce the dose, and result in good immunotherapeutic effects.