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.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Special Emphasis Panel (ZRG1-IDM-R (02))
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Watson, Bracie
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Nationwide Children's Hospital
United States
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McGillivary, Glen; Jordan, Zachary B; Peeples, Mark E et al. (2013) Replication of respiratory syncytial virus is inhibited by the host defense molecule viperin. J Innate Immun 5:60-71
Brockson, M Elizabeth; Novotny, Laura A; Jurcisek, Joseph A et al. (2012) Respiratory syncytial virus promotes Moraxella catarrhalis-induced ascending experimental otitis media. PLoS One 7:e40088
Grieves, Jessica L; Jurcisek, Joseph A; Quist, Brian et al. (2010) Mapping the anatomy of respiratory syncytial virus infection of the upper airways in chinchillas (Chinchilla lanigera). Comp Med 60:225-32
Bakaletz, Lauren O (2010) Immunopathogenesis of polymicrobial otitis media. J Leukoc Biol 87:213-22
Jewell, Nancy A; Vaghefi, Negin; Mertz, Sara E et al. (2007) Differential type I interferon induction by respiratory syncytial virus and influenza a virus in vivo. J Virol 81:9790-800
Durbin, Joan E; Durbin, Russell K (2004) Respiratory syncytial virus-induced immunoprotection and immunopathology. Viral Immunol 17:370-80