RSV Upper Airway Infection & Otitis Media

描述（由申请方提供）：呼吸道合胞病毒（RSV）是婴儿和老年人下呼吸道感染的主要原因。RSV引起的细支气管炎和肺炎是幼儿住院的主要原因。虽然原发性感染是最严重的，中和抗体的存在将防止肺部感染，但终生上呼吸道再感染是规律。虽然对上呼吸道RSV感染知之甚少，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。目前尚无RSV疫苗。RSV疫苗开发的进展受到新生儿接种疫苗固有问题（在2至4个月的原发性感染高峰之前）以及20世纪60年代福尔马林化全病毒疫苗试验期间疫苗增强疾病的遗留问题的阻碍。我们已经开发了小鼠和灰鼠模型的鼻咽和咽鼓管RSV感染，并开发了工具来研究它们。使用这些模型，我们将能够测试RSV在细菌性中耳炎（灰鼠）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学（小鼠），并测试这些候选疫苗预防病毒性和细菌性中耳炎（灰鼠）的能力。我们建议，可以使用一种疫苗，以防止上呼吸道感染的RSV在年龄较大的婴儿，以防止中耳炎，以及提供一些措施，防止下呼吸道疾病的幼儿和成人。

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.