Development of a non-living subunit rotavirus vaccine

描述(申请人提供)：婴幼儿轮状病毒病 全球100万人死亡，美国损失15亿美元 每年一次。1999年，FDA批准的唯一活的口服轮状病毒疫苗， 涉嫌造成肠梗阻，被从市场上撤回。我们有 开发了一种基于小鼠轮状病毒蛋白的亚单位疫苗原型。 在成年小鼠模型中进行的广泛的原则证明研究表明 该疫苗几乎完全阻止了轮状病毒在挑战后的脱落。 我们正在开发一种类似的人类轮状病毒株疫苗，用于最终 人类的口服分娩。因为疫苗的产量和质量需要 为了改进，这里提出了加强这两个方面的研究。在这项提案中，我们 将：(1)修饰亚单位疫苗编码基因，(2)生产和 对疫苗蛋白质进行量化，以证明其产量可以提高，以及(3) 用小鼠模型建立经修饰的小鼠的保护效果 疫苗保持不变，以确定最低疫苗剂量，并 在远缘繁殖的小鼠身上评估疫苗。在第二阶段SBIR研究中，我们将完善 疫苗的配制、给药和生产过程中的安全性和 免疫原性试验。在第三阶段SBIR研究中，我们将进行功效 在人体上进行试验，并寻求FDA的批准。 建议的商业应用： 全球每年有近100万婴儿死于轮状病毒引起的脱水。在美国 每年约有100人死亡，超过150万次医生就诊&5万人 医院入院。因此，轮状病毒在世界范围内引起发病率和死亡率。 世卫组织建议开发一种疫苗来呈现轮状病毒引起的 疾病。目前还没有安全有效的疫苗可用。这个 世界范围内的需求是巨大的，商业机会存在。

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 In 1999, the only FDA-approved live-oral rotavirus vaccine, which was implicated in causing bowel obstruction, was withdrawn from the market.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.