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. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC006468-02
Application #
6848059
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Watson, Bracie
Project Start
2004-01-27
Project End
2006-12-31
Budget Start
2005-01-01
Budget End
2005-12-31
Support Year
2
Fiscal Year
2005
Total Cost
$450,421
Indirect Cost
Name
Nationwide Children's Hospital
Department
Type
DUNS #
147212963
City
Columbus
State
OH
Country
United States
Zip Code
43205
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