Positive correlation trend between the dose of ag85a/bDNA vaccine and the immune effect.
At present, the effective dose of DNA vaccine IM immunized mice is
usually 100μg (31, 41). The results of our study confirmed that the
100μg DNA IM could significantly affect the differential expression of
host genes and changes in regulatory pathways. The lower than 100μg DNA
vaccine had little effect on differential gene expression and regulatory
pathways, and the higher than 100μg won’t lead to more significant
effects and make a waste of vaccine inversely. The results suggest that
it is necessary to explore the appropriate immunization dose to achieve
an effective intervention effect when different animals and humans are
IM immunized with DNA vaccines. The method of system biology will be
helpful to determine the effective dose in future clinical trials of DNA
vaccines.
EP immunization enhances the immune effect of the vaccine .
Our previous research showed that only 50μg of ag85a/b DNA
vaccine by EP immunization could reach the efficacy of 100μg DNA IM(31).
Other results of clinical trials or animal experiments have also
demonstrated that DNA vaccines, for example, from HIV (42), Zika virus
(43), Japanese encephalitis virus (44), and HPV (45), EP immunization
could improve the immune effect. From the gene transcriptome level, our
study reveals that 10μg DNA EP immunization could significantly affect
the differential expression of genes in the body. With the gradual
increase of DNA dose, the effects of DNA vaccine on DE gene number,
differential expression level, and regulatory pathways had not changed
obviously. But 50μg DNA EP immunization had the best efficacy, such as
the lowest number of bacterial colonies in organs, and the lowest lesion
area and degree (31). These results suggest that the effect of EP
immunization was also related to the DNA dose, but EP immunization could
improve the host immune efficiency more than IM immunization. A lower
dose of DNA EP could reach the same immune effect as a higher dose of
DNA IM, which can reduce the amount of DNA vaccine used. In addition, we
also found that the targets of DNA EP were highly consistent with those
of DNA IM, and the DE genes and regulatory pathways affected by the two
immunization methods of effective DNA doses were highly overlapping
(Fig. 3). Our study further proves that DNA EP immunization could
enhance the host’s immune response, but did not change its main targets
and mechanism of action(46).