Respiratory Syncytial Virus (RSV) is an important cause of morbidity and mortality in elderly adults and those with high-risk cardiopulmonary conditions. Among community dwelling elderly and high-risk persons, RSV infections can be documented in 3-10 percent of persons annually and influenza A in 0-5 percent. Among hospitalized persons, RSV accounts for 9.7 percent of admissions for acute respiratory disease in the winter, compared to 12.1 percent for influenza A. The clinical impact of the two viruses is similar. Although the presence of underlying disease and low serum neutralizing antibody titers is correlated with risk of hospitalization, other factors are likely to contribute to disease severity. Results in experimental animal models have convincingly demonstrated that cellular immune responses to RSV are determining factors in lung pathology following infection. Neither the pathogenesis nor the cellular immune response to RSV in elderly persons has been investigated. This research will investigate those factors associated with severe RSV infection in older persons. The primary hypothesis to be tested is that age-associated changes in the RSV-specific cellular immune response during infection lead to impaired clearance of virus and more severe disease in the elderly. The research will be conducted in RSV infected young and old adults with a spectrum of disease severity ranging from mild to severe. Measures of the innate and adaptive cellular and humoral immune response, the kinetics of viral clearance, and inflammatory markers will be examined in these persons when they are seen in physician's offices or admitted to the hospital with symptomatic RSV illnesses. The interrelationships between these factors, older age, the presence of underlying diseases, and RSV disease severity will be determined by multivariate analysis. Using this data, the contribution of each factor to disease severity can be estimated. An understanding of disease pathogenesis useful for guiding optimal approaches to novel therapies and in development of vaccines for RSV in this age group. Assessment of viral load and possible spread to the lower airways, as well as the pattern of viral clearance in older adults will be important to better predict whether antivirals or immunomodulators will be useful. Additionally, this information coupled with knowledge of the immune and inflammatory response to infection will better allow us to predict the type of vaccine, adiuvants and delivery systems required to prevent infection and disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI045969-06
Application #
6931510
Study Section
Epidemiology of Clinical Disorders and Aging Study Section (ECDA)
Program Officer
Rubin, Fran A
Project Start
1999-04-15
Project End
2009-07-31
Budget Start
2005-08-01
Budget End
2006-07-31
Support Year
6
Fiscal Year
2005
Total Cost
$553,944
Indirect Cost
Name
University of Rochester
Department
Internal Medicine/Medicine
Type
Schools of Dentistry
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627
Halliley, Jessica L; Tipton, Christopher M; Liesveld, Jane et al. (2015) Long-Lived Plasma Cells Are Contained within the CD19(-)CD38(hi)CD138(+) Subset in Human Bone Marrow. Immunity 43:132-45
Walsh, Edward E; Peterson, Derick R; Kalkanoglu, Aja E et al. (2013) Viral shedding and immune responses to respiratory syncytial virus infection in older adults. J Infect Dis 207:1424-32
Lee, F Eun-Hyung; Walsh, Edward E; Falsey, Ann R (2011) The effect of steroid use in hospitalized adults with respiratory syncytial virus-related illness. Chest 140:1155-1161
Lee, F Eun-Hyung; Halliley, Jessica L; Walsh, Edward E et al. (2011) Circulating human antibody-secreting cells during vaccinations and respiratory viral infections are characterized by high specificity and lack of bystander effect. J Immunol 186:5514-21
Lee, F Eun-Hyung; Falsey, Ann R; Halliley, Jessica L et al. (2010) Circulating antibody-secreting cells during acute respiratory syncytial virus infection in adults. J Infect Dis 202:1659-66
Halliley, Jessica L; Kyu, Shuya; Kobie, James J et al. (2010) Peak frequencies of circulating human influenza-specific antibody secreting cells correlate with serum antibody response after immunization. Vaccine 28:3582-7
Duncan, Coley B; Walsh, Edward E; Peterson, Derick R et al. (2009) Risk factors for respiratory failure associated with respiratory syncytial virus infection in adults. J Infect Dis 200:1242-6
Kyu, Shuya Y; Kobie, James; Yang, Hongmei et al. (2009) Frequencies of human influenza-specific antibody secreting cells or plasmablasts post vaccination from fresh and frozen peripheral blood mononuclear cells. J Immunol Methods 340:42-7
Walsh, Edward E; Peterson, Derick R; Falsey, Ann R (2007) Is clinical recognition of respiratory syncytial virus infection in hospitalized elderly and high-risk adults possible? J Infect Dis 195:1046-51
Walsh, Edward E; Falsey, Ann R (2004) Age related differences in humoral immune response to respiratory syncytial virus infection in adults. J Med Virol 73:295-9

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