Preclinical safety and tolerability of a repeatedly administered human leishmaniasis DNA vaccine

Riede, O; Seifert, K; Oswald, D; Endmann, A; Hock, C; Winkler, A; Salguero, F J; Schroff, M; Croft, S L; Juhls, C

MIDGE-Th1 vector DNA was not cleared from skin and inguinal lymph nodes within 60 days after four injections. Although this 20 This short time to overall clearance was probably related to wider dispersion of DNA upon multiple jet injection, the lower DNA concentration (five jet injections of 10 μg DNA at 1 mg ml − 1 versus one needle injection of 120 μg DNA at 4 mg ml − 1 ), as well as the rapid entry into the blood circuit due to the high vascularization and low retention rate of macromolecules in tumor tissue as compared with normal skin tissue. Though only a side-by-side comparison would be conclusive, we propose that these parameters strongly affected the time to overall clearance than the DNA dose. In fact, the rats in our study received up to 0.6 μg LEISHDNAVAX DNA per gram body weight, thus a lower relative DNA dose than that administered to mice of the referenced study (~1.6 μg tumor necrosis factor alpha MIDGE DNA per gram body weight). 20 A persistence of at least 60 days as observed in our study suggests that vector DNA had entered long-living cells residing in the skin. Whether or not this vector DNA is still functioning cannot be concluded from our results, as the quantitative PCR method targeted a short consensus sequence only.