RSV Upper Airway Infection and Otitis Media

RSV 上呼吸道感染和中耳炎

• 批准号: 7728249
• 负责人: Lauren O Bakaletz
• 金额: $ 43.84万
• 依托单位: RESEARCH INST NATIONWIDE CHILDREN'S HOSP
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-27 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7728249
• 关键词: Antigens; Bacteria; Biology; Bronchiolitis; Child; Chinchilla (genus); Clinical Data; Development; Disease; Elderly; Formalin; Grant; Health; Hospitalization; Host Defense; Human; Immune response; Immunity; Immunization; Inbred Strain; Infant; Infection; Intention; Life; Lower Respiratory Tract Infection; Lung; Modeling; Mus; Nature; Newcastle disease virus; Nose; Organism; Otitis Media; Pneumonia; Population; Predisposition; Preparation; Prevention strategy; Principal Investigator; Process; Recombinants; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory syncytial virus; Respiratory syncytial virus RSV F proteins; Rodent Model; Testing; Vaccines; Viral; Virus; Virus Diseases; ear infection; neutralizing antibody; novel vaccines; pathogen; prevent; programs; research study; response; vaccine candidate; vaccine development; vector

DESCRIPTION (provided by applicant): Respiratory Syncytial Virus (RSV) is a major cause of lower respiratory tract infection in infants and the elderly, and bronchiolitis and pneumonia caused by RSV are the primary reason for hospitalization of young children. For many years there has been an active search to find a safe and effective vaccine to prevent primary RSV infection in naWve infants, although progress in RSV vaccine development has been hampered by the unusual biology of the virus as well as the legacy of vaccine-enhanced illness during trials of a formalin-inactivated whole virus vaccine preparation in the mid 1960's. The problem of establishing RSV immunity is complicated by the fact that while the presence of neutralizing antibody is generally protective against pulmonary infection, re-infection of the upper airway throughout life is the rule. The observation that adaptive immune response fails to protect the upper airway is well established, but not well understood. While upper airway disease is never life threatening, it is nonetheless a very important health problem as RSV has been shown to be the predominant viral pathogen predisposing children to bacterial otitis media (OM). Since RSV is a major trigger for OM, and clinical data show frequent reinfection in young children, we hypothesize that development of an effective vaccine targeting RSV infection will have a significant impact on the occurrence of OM. In the first cycle of this grant we have developed both murine and chinchilla models of RSV upper airway infection, and have used these to test a new RSV vaccine candidate: a recombinant Newcastle disease virus vector expressing the RSV F protein. We have found that mucosal priming with this construct is protective in both rodent models, and now wish to explore both the mechanism of this protection as well as the ability of this vaccine to inhibit bacterial OM following viral and bacterial co- infection. Our specific aims are these: 1) Determine whether immunization against RSV can protect against bacterial co-infection in the chinchilla model; 2) Define the correlates of upper airway protection; and 3) Determine the mechanisms by which RSV infection enhances host susceptibility of bacterial OM. Recent studies have found that otitis media, or ear infections, in babies and young children are always caused by infection with both a viral and a bacterial organism. The bacteria that cause ear infections normally live in the nose, and are not a problem until the child catches a cold. Once the child has a virus infection, the host defenses are damaged, and normally harmless bacteria then cause disease. There is one cold virus called RSV which infects children over and over and is found in the majority of children with ear infections. Our group has found a new vaccine against this virus, and want to test whether immunity to RSV can protect against the process that causes bacterial ear infections.

描述（申请人提供）：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。多年来，人们一直在积极寻找一种安全有效的疫苗来预防初生婴儿的原发性 RSV 感染，尽管 RSV 疫苗开发的进展因病毒的不寻常生物学特性以及疫苗增强的遗留问题而受到阻碍。 1960 年代中期福尔马林灭活全病毒疫苗制剂试验期间患病。建立 RSV 免疫力的问题因以下事实而变得复杂：虽然中和抗体的存在通常可以防止肺部感染，但一生中上呼吸道的再次感染是常见的。适应性免疫反应无法保护上呼吸道的观察已得到充分证实，但尚未得到充分理解。虽然上呼吸道疾病不会危及生命，但它仍然是一个非常重要的健康问题，因为 RSV 已被证明是导致儿童患细菌性中耳炎 (OM) 的主要病毒病原体。由于 RSV 是 OM 的主要触发因素，并且临床数据显示幼儿中频繁再次感染，我们假设开发针对 RSV 感染的有效疫苗将对 OM 的发生产生重大影响。在本次资助的第一个周期中，我们开发了 RSV 上呼吸道感染的小鼠和龙猫模型，并使用这些模型来测试新的 RSV 候选疫苗：表达 RSV F 蛋白的重组新城疫病毒载体。我们发现用这种构建体进行的粘膜启动在两种啮齿动物模型中都具有保护作用，现在希望探索这种保护的机制以及这种疫苗在病毒和细菌共感染后抑制细菌 OM 的能力。我们的具体目标是： 1) 确定 RSV 免疫是否可以防止龙猫模型中的细菌混合感染； 2) 定义上呼吸道保护的相关因素； 3) 确定RSV感染增强宿主对细菌性OM的易感性的机制。 最近的研究发现，婴儿和幼儿的中耳炎或耳部感染总是由病毒和细菌感染引起。引起耳部感染的细菌通常生活在鼻子里，直到孩子感冒为止，这些细菌都不是问题。一旦孩子感染病毒，宿主的防御就会遭到破坏，通常无害的细菌就会致病。有一种名为 RSV 的感冒病毒会反复感染儿童，并且在大多数患有耳部感染的儿童中都存在这种病毒。我们的小组已经找到了一种针对这种病毒的新疫苗，并希望测试对 RSV 的免疫力是否可以预防导致细菌性耳部感染的过程。

项目成果

Respiratory syncytial virus promotes Moraxella catarrhalis-induced ascending experimental otitis media.

呼吸道合胞病毒促进卡他莫拉菌诱导的上行性实验性中耳炎。

• 发表时间: 2012
• 影响因子: 3.7
• 作者: Brockson, M Elizabeth;Novotny, Laura A;Jurcisek, Joseph A;McGillivary, Glen;Bowers, Martha R;Bakaletz, Lauren O
• 通讯作者: Bakaletz, Lauren O