Optimization of Rotavirus Vaccine Production

Rotavirus is the most common cause of debilitating diarrhea, dehydration and death in infants and young children around the globe. Currently approved live oral vaccines (Rotarix® and RotaTeq®) are only -50% or less effective in children from developing countries. This reduced efficacy is due to factors that decrease the effective titer of the virus reaching the gut, impairment of the host response of the infant and/or differences in virus and serotype distribution. In addition, both vaccines are associated with a low risk of diarrhea and intussusception among infants who receive the vaccine. It is critical that alternative approaches for a rotavirus vaccine be considered to improve the safety and efficacy of oral rotavirus vaccines. Rotavirus strain CDC-9 developed by the CDC is a viable vaccine candidate based on desirable patterns of potential attenuation, robust growth in cGMP qualified Vero cells, and proof of concept in pre-clinical studies. In this Phase I proposal, Meridian Life Science, Inc. will identify growth kinetics of the virus and develop robust downstream purification and heat-inactivation processes. The work described in this proposal will provide the framework for manufacture of clinical grade material for Phase I and Phase II human clinical trials.