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

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 DESCRIPTION (provided by applicant): Rotavirus is the leading cause of severe dehydrating diarrhea in children worldwide, and is responsible for an estimated 500,000 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 $1.00 per dose. This vaccine was developed as a public-private partnership project and is expected to receive India licensure in 2014 and WHO Prequalification in 2015 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 (1 hour or longer) exposure to 70°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 1) develop a formulation and process for manufacturing dry thermostable rotavirus vaccine using PBV technology, and 2) 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.