Nipah Virus Marker Vaccine and Companion Diagnostic Test

描述（由申请人提供）：尼帕病毒感染是一种新出现的人类和猪的疾病，在1998-1999年马来西亚的一次流行期间首次被描述。尼帕病毒在人类中引起脑炎，在猪和其他动物中引起呼吸和中枢神经系统疾病。该病毒和相关的亨德拉病毒是副粘病毒，不同于任何其他已确定的副粘病毒属，并被提议代表一个新属（亨尼帕病毒）的成员。目前还没有关于试图开发和评价针对这类新发现的病毒的疫苗的报告，这类病毒能够在人和动物中引起致命的脑炎。该项目的长期目标是开发一种活的金丝雀痘病毒载体，表达尼帕病毒的F和G蛋白，用作控制人和动物中尼帕病毒感染的疫苗。第二个目标是开发尼帕病毒感染的血清学诊断测定，可在生物安全等级2 （BSL2）条件下进行。目前的诊断方法需要在BSL4条件下培养尼帕病毒。这头猪将被用作测试金丝雀痘载体疫苗安全性和有效性的动物模型。这是适当的，因为猪对尼帕病毒感染非常敏感，而且在马来西亚疫情中，人类从受感染的猪身上感染了尼帕病毒。金丝雀痘病媒已成功地用于人类、猪和其他动物的疫苗。接种疫苗的猪应产生针对尼帕病毒F和G蛋白的中和抗体和记忆T细胞。感染尼帕病毒的猪也会产生针对核衣壳蛋白的抗体。利用杆状病毒载体中表达的N蛋白作为抗原，可以用ELISA法检测到N抗体。这将允许快速识别接种疫苗或未接种疫苗的猪，这些猪感染了野生型病毒。具有这些特征的疫苗和伴随诊断测试将在未来的根除计划中非常有用，因为它可以减少猪的感染，从而减少向其他猪和人类的传播，并减少疾病的社会、经济和环境影响。由于尼帕病毒和亨德拉病毒密切相关，这项工作将提供重要信息，有助于开发针对这一新型人畜共患副粘病毒成员的安全有效的人类疫苗。

DESCRIPTION (provided by applicant): Nipah virus infection is an emerging new disease of humans and swine, first described during a 1998-1999 epidemic in Malaysia. The Nipah virus causes encephalitis in humans and respiratory and central nervous system disease in swine and other animals. This virus and the related Hendra virus are paramyxoviruses that are distinct from any of the other established genera of paramyxoviruses and have been proposed to represent members of a new genus (Henipavirus). There have been no reports of attempts to develop and evaluate vaccines against this newly discovered group of viruses, which are capable of causing fatal encephalitis in man and animals. The long-term objective of this project is to develop a live canarypox virus vector expressing the F and G proteins of the Nipah virus for use as a vaccine to control Nipah virus infection in man and animals. A second objective is to develop a serologic diagnostic assay for Nipah virus infection, which can be performed under biosafety level 2 (BSL2) conditions. Current diagnostic assays require growing the Nipah virus under BSL4 conditions. The pig will be used as the animal model for testing the safety and efficacy of the canarypox vectored vaccine. This is appropriate because the pig is very susceptible to infection with Nipah virus and because in the Malaysian outbreak humans contracted Nipah virus infection from infected pigs. The canarypox vector has been successfully used as a vaccine in humans, pigs and other animals. Vaccinated pigs should develop neutralizing antibodies and memory T cells to the Nipah F and G proteins. Pigs that become infected with Nipah virus will also develop antibodies against the nucleocapsid (N) protein. Antibodies to N can be detected with an ELISA assay using the N protein expressed in a baculovirus vector as the antigen. This would allow for the rapid identification of vaccinated or unvaccinated pigs, which become infected with the wild type virus. A vaccine and companion diagnostic test with these attributes would be very useful in future eradication programs by reducing infection in pigs, thereby reducing transmission to other pigs and humans and reducing the social, economic, and environmental impact of the disease. Since Nipah and Hendra viruses are closely related, this work will provide important information relative to the potential for development of safe and effective vaccines for humans against members of this novel group of emerging zoonotic paramyxovirus.