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

To assess toxicity of LEISHDNAVAX in naive mice, sterile phosphate-buffered saline (PBS, placebo) and ascending doses of the vaccine were injected either once or five times in weekly intervals (Table 1) . LEISHDNAVAX was well tolerated at all doses tested. No animal died during the in-life phase, and no change in behavior or external appearance of the animals was noted. Comparing placebo-treated to LEISHDNAVAX-treated animals, no differences were observed in body weight, food and drinking water consumption, ophthalmological and auditory examinations, urinalysis, organ weights and the neurological screening. No local intolerance reactions were noted after single or repeated vaccine dosing. Minor deviations in single animals/groups for few blood parameters (large unstained cells, albumin/globulin ratio, αamylase) were classified as not vaccine-related. Macroscopic post mortem examination of organs revealed an enlarged spleen in a single male animal 1 day after single administration of 100 μg LEISHDNAVAX, which possibly indicated the activation of the lymphatic system. In all animals the histological findings were within the normal range of variation. No LEISHDNAVAX-related morphological lesions were found. No signs of auto-immune reactions were observed, and there were no elevated levels of serum antibodies against dsDNA detected.