Non-Clinical Safety Assessment of Single and Repeated Administration of Hepatitis B (rDNA) Vaccine

Abstract

Hepatitis B infection is an important public health concern all over the world. As no specific treatment is available, greatest emphasis is placed on prevention through immunization. A recently developed Hepatitis B (rDNA) vaccine, containing purified surface antigen of virus like particles derived from culturing genetically engineered Hansenula polymorpha yeast cells having the Hepatitis B surface antigen gene of Hepatitis B virus was evaluated to establish potential safety and tolerability of the Hepatitis B (rDNA) vaccine formulation. Non clinical safety assessment was evaluated as single dose studies in mice and rats and a repeat dose study in rats. No signs of acute toxicity were noted in mice and rats through clinical signs and gross necropsy examination. The local reactions observed in both the species at the injection site were attributed to the property of an adjuvanted vaccine. Similarly, the absence of systemic toxicity was evaluated after repeated administrations in the rat. In repeated dose study, additionally histiocytosis and/or lymphoid hyperplasia at femoral lymph node were observed. The incidences of such local effects were considered as innate immune response generated against the vaccine antigens and enhanced by the adjuvants. The vaccine was shown to be well tolerated without any obvious signs of adverse systemic toxicity, with findings largely attributable to the adjuvant used. The immunogenicity profile showed measurable antibody titer. Therefore, in these non-clinical models, the single and repeated dose administrations of Hepatitis B (rDNA) vaccine were considered as well tolerated up to absolute human dose (1 ml).