Development of a thermostable rotavirus vaccine for mucosal delivery without need for reconstitution

DESCRIPTION provided by applicant Rotavirus is the leading cause of severe dehydrating diarrhea in children worldwide and is responsible for an estimated deaths each year mostly in children under the age of five years in developing countries Recently two live rotavirus vaccines RotaTeq Merck and Rotarix Glaxo Smith Kline have been approved for use in infants Importantly both transportation and storage of these vaccines require a cold chain and in their current multi dose liquid formulations the storage space requirements for these vaccines are five to twenty times higher than for polio vaccine Thus there is an urgent need to develop a cost effective rotavirus vaccine that is dry ambient temperature stable potent and does not require reconstitution Bharat Biotech has developed a live attenuated rotavirus vaccine Rotavac and plans to sell it to global public markets at a price of US $ per dose This vaccine was developed as a public private partnership project and is expected to receive India licensure in and WHO Prequalification in for supply to UN agencies Clinical studies with Rotavac have demonstrated safety immunogenicity and efficacy in Indian children when administered orally in three doses however Rotavac must be refrigerated to maintain stability Universal Stabilization Technologies Inc UST has developed and proven commercial value of its innovative patent pending Preservation by Vaporization PBV technology UST has demonstrated that many biologicals including live viruses and bacteria as well as antibodies enzymes coagulation factors and other proteins retain high activity and long term stability at ambient temperatures after processing by PBV and can survive short term hour or longer exposure to C or higher temperatures The proposed technology development a dry thermostable quick dissolving oral buccal film formulation of Rotavac will allow cheaper vaccine production because of the enhanced yields possible with PBV as well as reduced distribution and storage costs because PBV formulations do not require a cold chain Further cost savings will be achieved by formulating the dry thermostable Rotavac vaccine as a quick dissolving film for oral administration A film formulation will also provide more accurate dosing and easier administration to infants than the current liquid formulations on the market The specific objectives of this Phase I project are develop a formulation and process for manufacturing dry thermostable rotavirus vaccine using PBV technology and manufacture quick dissolving films containing dry thermostable rotavirus vaccine suitable for oral delivery In Phase II of this project UST will assess the immunogenicity and protective effects of the quick dissolving film formulation of dry thermostable rotavirus vaccine in animal models The long term goal of this project is to generate a quick dissolving film formulation of rotavirus vaccine fr oral delivery to infants that is ambient temperature stable immunogenic protective and low cost to manufacture store and ship PUBLIC HEALTH RELEVANCE Rotavirus RV is the leading cause of severe dehydrating diarrhea in children worldwide and although there are currently two licensed vaccines on the market they must be refrigerated during transportation and storage and are administered as an oral liquid These vaccines are costly have short shelf lives at ambient temperatures and are not easy to administer to infants all of which are challenges in developing regions of the world where the rotavirus disease burden is highest We have developed technology for making vaccines stable at ambient temperatures and we will use this technology to generate a potent ambient temperature stable rotavirus vaccine formulation that can be easily administered to infants as a quick dissolving oral film