Recombinant Subunit West Nile Virus Vaccine Development

描述（由申请方提供）：本项目的总体目标是开发重组WN（WN）病毒亚单位疫苗的生产工艺，以预防危及生命的WN病毒感染。WN病毒于1999年首次在北美分离出来。在不到三年的时间里，该病毒的地理分布在美国急剧扩大。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、兔和马中诱导病毒中和抗体，在WN病毒感染的鼠模型中保护免受感染。拟议的临床前研发活动将根据药品生产质量管理规范（cGMP）和药物非临床研究质量管理规范（GLP）生产候选疫苗。目的是生产适合I期临床试验的疫苗。具体目标包括工艺开发、佐剂制剂、动物模型中的安全性、免疫原性和有效性评价以及研究性新药申请的准备。该项目将为临床医生和公共卫生官员提供管理WN病毒爆发的新方法。

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.