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

Abstract

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 2×104 colony-forming units (CFUs) of MTB H37Rv through tail vein injection, then was treated with 10μg, 50μg, 100μg, and 200μg 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-γ+ T cells% in whole blood from 200 µg DNA IM group and four DNA EP groups increased significantly (P<0.05), CD8+IFN-γ+ T cells% (in 200 μg DNA EP group), CD4+IL-4+ T cells% (50 μg DNA IM group) and CD8+IL-4+ T cells% (50 μg and 100 μg DNA IM group, 100 μg and 200 μg 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 μg 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 μg DNA IM group and 50 μg 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.

Preventive effects of Mycobacterium tuberculosis DNA vaccines on the mouse model with latent tuberculosis infection

“…After the supernatant was aspirated, 500 µl PBS was pipetted and analyzed within 1 h by FACS Canto II flow cytometry (BD Pharmingen) and FACS Diva software. The representing FACS graphs with the gating method were described in our previous study ( 33 ).…”

B21 DNA vaccine expressing ag85b, rv2029c, and rv1738 confers a robust therapeutic effect against latent Mycobacterium tuberculosis infection

“…DNA vaccines expressing latent antigens have also been shown to effectively induce Th1-type immune responses (16,17). In addition, immunotherapy with plasmid DNA has been found to provide effective adjuvant therapy in mice in combination with chemotherapy (18,19). Antigen fusion in various TB-containing latency-related antigens has also been explored as a vaccine target.…”

“…Among the many vaccines explored, Ag85A and Ag85B have been widely used as acute phase antigens, and related DNA vaccines have been demonstrated to have immunotherapeutic effects in mice (19,22). Rv2029c (pfkB) is a member of the DosR regulator family and is upregulated during hypoxia and in macrophages (23).…”

B21 DNA vaccine expressing ag85b, rv2029c, and rv1738 confers a robust therapeutic effect against latent Mycobacterium tuberculosis infection

“…DNA vaccines expressing latent antigens have also been shown to effectively induce Th1-type immune responses ( 16 , 17 ). Additionally, it has been discovered that immunotherapy using plasmid DNA is an efficient adjuvant therapy in mice when combined with chemotherapy ( 18 , 19 ). Antigen fusion in various TB-containing latency-related antigens has also been explored as a vaccine target.…”

“…Among the many vaccines explored, Ag85A and Ag85B have been widely used as acute phase antigens, and related DNA vaccines have been demonstrated to have immunotherapeutic effects in mice ( 19 , 22 ). Rv2029c (pfkB) is a member of the DosR regulator family and is upregulated during hypoxia and in macrophages ( 23 ).…”