AUTHOR=Liang Yan , Cui Lei , Xiao Li , Liu Xiao , Yang Yourong , Ling Yanbo , Wang Tong , Wang Lan , Wang Jie , Wu Xueqiong 

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

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.876579

DOI=10.3389/fimmu.2022.876579

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>Tuberculosis (TB) is a major global public health problem. New treatment methods on TB are urgently demanded.</p></sec><sec><title>Methods</title><p>Ninety-six female BALB/c mice were challenged with 2×10<sup>4</sup> colony-forming units (CFUs) of MTB H<sub>37</sub>Rv through tail vein injection, then was treated with 10μg, 50μg, 100μg, and 200μg of <italic>Mycobacterium tuberculosis</italic> (MTB) <italic>ag85a/b</italic> chimeric DNA vaccine delivered by intramuscular injection (IM) and electroporation (EP), respectively. The immunotherapeutic effects were evaluated immunologically, bacteriologically, and pathologically.</p></sec><sec><title>Results</title><p>Compared with the phosphate-buffered saline (PBS) group, the CD4<sup>+</sup>IFN-γ<sup>+</sup> T cells% in whole blood from 200 µg DNA IM group and four DNA EP groups increased significantly (<italic>P</italic>&lt;0.05), CD8<sup>+</sup>IFN-γ<sup>+</sup> T cells% (in 200 μg DNA EP group), CD4<sup>+</sup>IL-4<sup>+</sup> T cells% (50 μg DNA IM group) and CD8<sup>+</sup>IL-4<sup>+</sup> 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 (<italic>P</italic>&lt; 0.05). The CD4<sup>+</sup>CD25<sup>+</sup> Treg cells% decreased significantly in all DNA vaccine groups (<italic>P</italic>&lt;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 (<italic>P</italic>&lt;0.001, <italic>P</italic>&lt;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.</p></sec><sec><title>Conclusions</title><p>An MTB <italic>ag85a/b</italic> 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 <italic>ag85a/b</italic> chimeric DNA vaccine.</p></sec>