Karolinska Institute, Sweden
Stefan Petkov has completed the first year of his PhD studies at Karolinska Institute and is currently working on the application of non-invasive optical imaging for evaluation of DNA vaccine performance.
Optical in vivo imaging is an attractive way of assessing gene expression due to its non-invasive nature and low cost. It is a powerful way to study the kinetics of expression of reportable genes, which makes it suitable for evaluation of the in vivo efficiency of genetic vaccines. Bioluminescence imaging is optimal for in vivo monitoring of both the reporter gene expression and the immune eradication of the reporter-expressing cells. We have previously shown that co-injection of luciferase (Luc) gene reporter together with DNA-immunogen leads to immune clearance of Luc/reporter-expressing cells, which correlates with a potent anti-immunogen response of both CD4+ and CD8+ T-cells. Little is, however, known about the effects of the type of immune response on the dynamics of this clearance. To address this, we have immunized BALB/c mice intradermally with DNA-immunogens inducing strong Th1- (HIV-1 protease, PR) or Th2-shifted immune response (HIV-1 reverse transcriptase, RT). Expression of the reporter was first registered 2 hours after delivery and followed for the next 21 days. Expression kinetics were identical up to day 9 post immunization. From day 9 signal in Th2-type responding RT-immunized mice decreased significantly faster compared to the signal registered in Th1-type responding PR-mice. Statistically significant correlations were found between bioluminescence intensity and Th-profile and potency of immunogen-specific cellular responses. Collectively, these results indicate that in vivo imaging data can substitute in vitro immunoassays and predict the outcome of DNA-immunizations already at an early stage.