Vol. 52, No. 1, 2009 - Alpha Chi

DNA Va c c i n e s f o r HIV
Results
In the study, we sought to optimize EP conditions for ID+EP immunization and to
determine if similar increases in immunogenicity could be achieved with ID immunizations
with EP in a non-human primate model. IFNγ ELISpot analysis showed that EP enhanced
the induction of cellular immune responses by 33 percent and that this response was seen
in the memory cell populations as there were twice as many IFNγ-producing cells in the
ID/+EP group compared to the ID group (figures 4 and 5 respectively). 12
Skin, as a target organ for plasmid injection and EP, has been used in only a small
number of vaccination trials. In these experiments, we used micro-electrodes (µEP) for
delivery into the ID compartment and compared the resulting immune response to those
achieved after IM+EP (Table 1). 12 We have shown that the use of µEP resulted in excellent
delivery, plasmid expression and induction of cellular and humoral responses in two large
animal models, pig and non-human primates.
As with IM electroporation, ID+EP was able to induce high levels of antibody titers
compared to needle injection (Table 1). Gag specific antibody titers were found to be 10-
fold greater than the env (data not shown). The higher gag titers are consistent with previous
IM+EP data from our lab. To further assess the induction of a Th2 mediated immune
response, measured by IL-4 ELISpot (Figure 6). The lack of IL-4 responses suggests that
HIV immunization with plasmid IL-12 by the ID route results in a Th1 mediated response.
When compared to previous data from our lab, as well as other IM+EP studies in
non-human primates, ID+EP seems to induce similar levels of cellular immune responses
through the first two immunizations at adapted plasmid doses. However, in this study we did
not see further boosting in IFNγ-producing cells. 12
We have attempted to modify the electrode configuration and pulse pattern for ID
immunization. Though further optimization is necessary, our studies show that DNA
delivery to the ID compartment could be useful for DNA vaccinations. In the future we hope
to better characterize the immune responses induced by ID+EP vaccination and examine
more in-depth aspects CD8 T-cell polyfunctionality using flow cytometry.
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Table 1. Comparison of immune responses induced by electroporation with IM or ID.
Figure and caption taken from Hirao et al., 2007, with permission. 12
IFNγ ELISpot and HIV gag ELISA results were taken after 3 doses at 1.0 mg/ antigen.