Immunotherapeutic mechanisms of ag85a/b DNA vaccine and its recovery
effect on M. tuberculosis-induced injury
Our previous research developed a novel tuberculosis (TB) DNA vaccine
ag85a/b showed a significant therapeutic effect on the mouse
tuberculosis model by intramuscular injection (IM) and electroporation
(EP). However, the action mechanisms between these two vaccine
immunization methods remain unclear. In a previous study, 96 M.
tuberculosis (MTB) H37Rv-infected BALB/c mice were treated with PBS,
10μg, 50μg, 100μg, and 200μg ag85a/b DNA vaccine delivered by IM and EP
three times at two-week intervals, respectively. In this study,
peripheral blood mononuclear cells (PBMCs) from 3 mice in each group
were isolated to extract total RNA. The gene expression profiles were
analyzed using gene microarray technology to obtain differentially
expressed (DE) genes. Finally, DE genes were validated by real-time
reverse transcription-quantitive PCR (RT-qPCR) and the GEO database.
After MTB infection, most of the up-regulated DE genes were related to
the digestion and absorption of nutrients or neuroendocrine, for
example, Iapp, Scg2, Chga, Amy2a5, etc, and most of the down-regulated
DE genes were related to cellular structural and functional proteins,
especially the structure and function proteins of alveolar epithelial
cell, for example, Sftpc, Sftpd, Pdpn, etc. Most of the abnormally
up-regulated or down-regulated DE genes in the TB model group were
recovered in the 100μg and 200μg ag85a/b DNA IM groups and four DNA EP
groups. The pancreatic secretion pathway down-regulated and Rap1 signal
pathway up-regulated had particularly significant changes during the
immunotherapy of the ag85a/b DNA vaccine on the mouse TB model. The
action target and mechanism of IM and EP are highly consistent.
Tuberculosis infection caused rapid catabolism and slow anabolism in
mice. For the first time, we found that the effective dose of the
ag85a/b DNA vaccine immunized whether by IM or EP could significantly
up-regulate immune-related pathways and recover the metabolic disorder
and the injury caused by MTB.