Needle-Free Delivery of Subunit Rotavirus Vaccines

描述（由申请人提供）：轮状病毒是婴儿严重胃肠炎的最常见原因，在全世界造成近100万人死亡，每年给美国造成15亿美元的损失。唯一一种FDA批准的轮状病毒疫苗因与肠梗阻（肠套叠）有关而于1999年被撤回。我们正在开发亚单位轮状病毒疫苗，其中一种含有强大的细菌肠毒素佐剂LT（R192G）。当在小鼠中鼻内或口服递送时，该疫苗制剂诱导几乎完全的保护作用，以防止口服攻击后的轮状病毒脱落。为了增加该候选疫苗的安全性和易于递送，我们建议使用小鼠模型在皮肤处比较三种无针免疫方法：（1）蛋白质制剂的局部施用（经皮免疫），（2）使用无针注射装置递送蛋白质制剂，和（3）使用注射装置递送DNA形式的制剂。每种交付方式将包括LT（R192G）。在II期SBIR研究中，我们将改进和制备最有效的疫苗制剂，用于人体初步安全性研究。 在III期SBIR研究中，我们将继续进行人体安全性、免疫原性和有效性试验，并寻求FDA批准。成功开发基于VP6的疫苗对社会和商业意义都很重要。

DESCRIPTION (provided by applicant): Rotavirus is the most common cause of severe gastroenteritis in infants causing nearly 1 million deaths worldwide and costing the United States 1.5 billion dollars annually. The only FDA-approved rotavirus vaccine was withdrawn in 1999 because of its association with bowel obstruction (intussusception). We are developing subunit rotavirus vaccines, one of which contains the powerful bacterial enterotoxin adjuvant LT(R192G). When delivered intranasally or orally in mice, this vaccine formulation induces nearly complete protection against rotavirus shedding after oral challenge. To increase the safety and ease of delivery of this candidate vaccine, we propose to compare three needle-free immunization methods at the skin using the mouse model: (1) Topical application (transcutaneous immunization) of the protein formulation, (2) Delivery of the protein formulation using a needleless injecting device, and (3) Delivery of a DNA form of the formulation using the injection device. Each delivery method will include LT(R192G). In Phase II SBIR studies, we will refine and prepare the most effective vaccine formulation for initial safety studies in humans. In Phase III SBIR studies, we will continue safety, immunogenicity and efficacy trials in humans and seek FDA approval. Successful development of VP6-based vaccines would be important for society and commercially significant.