DNA vaccination for rabies: Evaluation of preclinical safety and toxicology

Abstract

The worldwide incidence of rabies and high rates of therapy failure, despite availability of effective vaccines indicate the need for timely and improved prophylactic approaches. DNA vaccination based on optimized formulation of lysosome-targeted glycoprotein of the rabies virus provides potential platform for preventing and controlling rabies. As per the pre-clinical requirements, listed in guidelines of Schedule Y, FDA and that of The European Agency for evaluation of Medicinal Products; we evaluated the acute (single dose – 14 days) using three dosing levels, that is, the therapeutic (1×), average (5×) and high dose (10×) intramuscular toxicity in the rodent model Swiss Albino mice. Furthermore, the chronic intramuscular toxicity (repeated dose – 43 days with another 14 days for satellite groups) was investigated using broad dosing levels ranging from low (7×), mid (14×) to high (28×) in Wistar rats. A range of parameters including physical, physiological, clinical, immunological, hematological along with histopathology profiles of target organs was monitored to assess the impact of vaccination. There were no observational adverse effects despite high dose administration of the DNA vaccine formulation. Thus, this study indicates the safety of next generation of vaccines as well as highlights their potential application.