Vaccination Against West Nile Virus

描述(由申请人提供)：本项目的总体目标是开发一种商业上可行的重组亚单位疫苗来预防西尼罗河病毒感染。1999年，西尼罗河病毒首次在北美被分离出来。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。第一阶段研究研究了基于美国西尼罗河病毒分离株包膜蛋白的免疫原。我们制备了重组蛋白和合成肽抗原，并启动了免疫研究。用重组抗原免疫小鼠，检测抗体反应，并进行保护性免疫试验。第二阶段的实验将给马接种一种很有希望的候选疫苗，并证明接种疫苗会引起保护性抗体。实验旨在利用我们的重组包膜蛋白抗原和氢氧化铝佐剂诱导高滴度抗体。随后的实验将确定在马身上诱导的抗体是否可以：(1)在体外中和西尼罗河病毒；(2)保护被动免疫的小鼠免受西尼罗河病毒的侵袭。该项目将为兽医、临床医生和公共卫生官员提供管理西尼罗河病毒暴发的新手段。

DESCRIPTION (provided by applicant): A commercially viable recombinant subunit vaccine to prevent West Nile virus infection is the overall objective of this project. West Nile 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. Phase I research studied immunogens based on the envelope protein of a U.S. West Nile virus isolate. We prepared recombinant protein and synthetic peptide antigens, and initiated immunization studies. Mice were vaccinated with the recombinant antigens, antibody responses were evaluated, and protective immunity was characterized. Phase II experiments will vaccinate horses with a promising candidate vaccine, and demonstrate that vaccination elicits protective antibodies. Experiments are designed to elicit high titer antibodies using our recombinant envelope protein antigen with aluminum hydroxide adjuvant. Subsequent experiments will determine if antibodies induced in horses can: (1) neutralize West Nile virus in vitro; (2) protect passively immunized mice from West Nile virus. This project will provide veterinarians, clinicians and public health officials with new means to manage West Nile virus outbreaks.