RSV Upper Airway Infection & Otitis Media

描述（由申请人提供）：呼吸道合胞病毒（RSV）是婴幼儿和老年人下呼吸道感染的主要原因。呼吸道合胞病毒引起的毛细支气管炎和肺炎是幼儿住院的主要原因。虽然初次感染最严重，中和抗体的存在可以防止肺部感染，但在整个生命过程中，上呼吸道的再感染是规律。虽然对上呼吸道RSV感染的了解相对较少，但最近的文献支持RSV可能是细菌性中耳炎易感性方面的主要病毒病原体的观点。目前没有RSV疫苗可用。呼吸道合胞病毒疫苗开发的进展一直受到新生儿疫苗接种固有问题（在2至4个月的原发性感染高峰之前）以及20世纪60年代正式全病毒疫苗试验期间疫苗增强疾病遗留问题的阻碍。我们建立了小鼠和栗鼠的鼻咽和咽鼓管RSV感染模型，并开发了研究工具。利用这些模型，我们将能够测试RSV在细菌性中耳炎（栗鼠）中的作用，开发候选疫苗，这些候选疫苗将提供针对RSV的粘膜和CTL免疫，而不会引起严重的免疫病理（小鼠），并测试这些候选疫苗预防病毒性和细菌性中耳炎（栗鼠）的能力。我们建议，一种预防RSV上呼吸道感染的疫苗可以用于年龄较大的婴儿，以预防中耳炎，并为幼儿和成人的下呼吸道疾病提供一定程度的保护。

DESCRIPTION (provided by applicant): Respiratory syncytial virus (RSV) is a major cause of lower respiratory infections in infants and the elderly. Bronchiolitis and pneumonia caused by RSV are the primary reasons for hospitalization of young children. While the primary infection is the most serious, and the presence of neutralizing antibody will protect against pulmonary infection, re-infection of the upper airway throughout life is the rule. Although relatively little is known about RSV infection of the upper respiratory tract, recent literature supports the idea that RSV may be the predominant viral pathogen in terms of predisposition to bacterial otitis media. Currently no RSV vaccine is available. Progress in RSV vaccine development has been hampered by the problems inherent in vaccinating newborns (before the peak of primary infection at 2 to 4 months), as well as the legacy of vaccine-enhanced illness during trials of a formalinized whole virus vaccine in the 1960s. We have developed mouse and chinchilla models of nasopharyngeal and Eustachian tube RSV infection, and developed tools to study them. Using these models we will be able to test the role of RSV in bacterial otitis media (chinchilla), develop vaccine candidates that will provide mucosal and CTL immunity against RSV without causing severe immunopathology (mouse), and test the ability of these candidates to protect against viral and bacterial otitis media (chinchilla). We suggest that a vaccine to prevent upper airway infection by RSV could be used in older infants to prevent otitis media as well as providing some measure of protection against lower airway disease in young children and adults.