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

Assessment of vaccine toxicity. The study was performed in accordance with GLP Regulations principles and German animal welfare regulations at LPT Laboratory of Pharmacology and Toxicology, Hamburg, Germany with prior approval by LPT's institutional animal care and use commissary (study no. 26814) and by the competent authority (Behörde für Gesundheit und Verbraucherschutz, Amt für Verbraucherschutz Lebensmittelsicherheit und Veterinärwesen, Billstraße 80, 20539 Hamburg, Germany, V 11307-591-00.33). One hundred and forty BALB/c mice (70 male, 70 female) were randomized and allocated to study groups. Animals were housed individually. At first treatment mice were 44-49 days (males) or 60-65 days (females) of age with a body weight of 18.2-22.5 g (males) or 18.0-20.4 g (females). Ten animals each (five per sex) received one i.d. needle injection (volume: 25 μl) into the dorsal tail base with a dose of 10, 50 or 100 μg LEISHDNAVAX or the placebo (PBS). They were killed 24 h post injection for evaluation of acute toxic reactions. Thirty animals each receiving placebo and 100 μg dose, or 20 animals each receiving 10 μg and 50 μg dose (injection volume: 25 μl) were injected by needle i.d. into the dorsal tail base five times in weekly intervals. Animals were killed after a recovery period of 24 h, 14 days or 61 days (placebo and 100 μg dose group only) following the fifth injection (Table 1) .