Recombinant Subunit West Nile Virus Vaccine Development

描述(申请人提供)：该项目的总体目标是开发一种重组WN(WN)病毒亚单位疫苗的制造工艺，以防止危及生命的WN病毒感染。1999年在北美首次分离到WN病毒。在不到三年的时间里，病毒在美国的地理分布急剧扩大。随着这种新出现的病原体在非洲大陆流行，疫苗将是对其他公共卫生措施的重要补充。先前的工作建立了生产重组WN病毒包膜蛋白亚单位疫苗的实验室工艺。候选疫苗在小鼠、兔子和马中诱导病毒中和抗体，在WN病毒感染的小鼠模型中保护免受感染。拟议的临床前研究和开发活动将根据良好制造规范(CGMP)和良好实验室规范(GLP)生产候选疫苗。其目标是生产适合第一阶段临床试验的疫苗。具体目标包括过程开发、佐剂配方、在动物模型中评估安全性、免疫原性和有效性，以及准备研究性新药申请。该项目将为临床医生和公共卫生官员提供管理WN病毒暴发的新手段。

DESCRIPTION (provided by applicant): The overall goal of this project is to develop a manufacturing process for a recombinant WN (WN) virus subunit vaccine to prevent life-threatening WN virus infections. WN virus was isolated for the first time in North America in 1999. In less than three years, the geographical distribution of the virus expanded dramatically in the United States. A vaccine will be an important complement to other public health measures as this emerging pathogen becomes endemic in this continent. Prior work established a laboratory process for producing a recombinant WN virus envelope protein subunit vaccine. The candidate vaccine induces virus-neutralizing antibodies in mice, rabbits and horses that protect against infection in a murine model of WN virus infection. The proposed preclinical research and development activities will produce the candidate vaccine under Good Manufacturing Practice (cGMP) and Good Laboratory Practice (GLP). The objective is to produce vaccine suitable for Phase I clinical trials. Specific aims include process development, formulation with adjuvant, evaluation of safety, immunogenicity and efficacy in animal models, and preparation of an Investigational New Drug Application. This project will provide clinicians and public health officials with new means to manage WN virus outbreaks.