Development of a non-living subunit rotavirus vaccine

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DESCRIPTION (Provided by Applicant): Rotavirus disease in infants causes nearly one million deaths worldwide and costs the United States 1.5 billion dollars annually. In 1999, the only FDA-approved live-oral rotavirus vaccine, which was implicated in causing bowel obstruction, was withdrawn from the market. We have developed a prototype subunit vaccine based on a mouse rotavirus protein. Extensive proof-of-principle studies in the adult mouse model demonstrated that the vaccine almost completely prevented rotavirus shedding following challenge. We are developing a similar vaccine from a human rotavirus strain for eventual oral delivery in humans. Because the vaccine yield and quality needs improvement, studies are proposed here to enhance both. In this proposal, we will: (1) modify the gene encoding the subunit vaccine, (2) produce and quantify the vaccine protein to prove that its yield can be enhanced, and (3) use the mouse model to establish that the protective efficacy of the modified vaccine remained unchanged, to determine the lowest vaccine dose, and to evaluate the vaccine in outbred mice. In Phase II SBIR studies, we will refine the vaccine formulation, administration and production process for safety and immunogenicity trials. In Phase III SBIR studies, we will conduct efficacy trials in humans and seek FDA approval. PROPOSED COMMERCIAL APPLICATION: Globally nearly 1 million infants die annually from rotavirus-induced dehydration. In the U.S. there are about 100 deaths per year with more than 1/2 million physician visits & 50,000 hospital admissions. Therefore, rotavirus causes both morbidity & mortality worldwide. WHO has recommended the development of a vaccine to present the rotavirus-caused disease. Currently there are no vaccines available that are safe and effective. The worldwide need is significant and the commercial opportunity exists.