Needle-Free Delivery of Subunit Rotavirus Vaccines

描述(申请人提供)：轮状病毒是婴儿严重胃肠炎的最常见原因，导致全球近100万人死亡，每年给美国造成15亿美元的损失。FDA批准的唯一轮状病毒疫苗于1999年被撤回，因为它与肠梗阻(肠套叠)有关。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)。当该疫苗经鼻腔或口服给药时，对口服攻击后的轮状病毒脱落具有几乎完全的保护作用。为了提高这种候选疫苗的安全性和易用性，我们建议使用小鼠模型比较三种无针免疫方法：(1)局部应用(经皮免疫)蛋白质配方，(2)使用无针注射装置输送蛋白质配方，以及(3)使用注射装置输送DNA形式的配方。每种交付方式都将包括LT(R192G)。在第二阶段的SBIR研究中，我们将提炼和准备最有效的疫苗配方，用于初步的人体安全性研究。在第三阶段SBIR研究中，我们将继续在人体上进行安全性、免疫原性和有效性试验，并寻求FDA的批准。成功开发基于VP6的疫苗将对社会具有重要的社会意义和商业意义。

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 The only FDA-approved rotavirus vaccine was withdrawn in 1999 because of its association with bowel obstruction (intussusception).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.