Abstract

Respiratory Syncytial Virus (RSV) causes severe disease in the elderly. The pathogenesis of severe disease in the elderly is probably multi-factorial but the dysregulation of the aging immune response is central to understanding disease severity. Unlike other viruses, RSV has evidence of typel and type2 responses. Typel responses include IFNg and IL-12 which are important in viral clearance. Type2 responses include IL-4, IL-5, and IL-10 secretion and are important in anti-parasitic responses, allergy and vigorous antibody production. We recently demonstrate that RSV-specific IL-5 (type2) responses during active infection correlate with symptom severity in young and middle-aged adults. We believe that RSV-IL-5 responses will play an important role in RSV disease severity in the elderly. RSV-specific antibody responses to infection are increased compared to young adults. We propose to study the role as well as the potential links between type2 cytokines and vigorous antibody responses in the elderly during RSV infection. The goal of our studies is to provide insights in prevention and treatment of severe RSV disease in the elderly. ? ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
1K23AI067501-01A1
Application #
7144865
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Cho, David
Project Start
2006-07-15
Project End
2011-06-30
Budget Start
2006-07-15
Budget End
2007-06-30
Support Year
1
Fiscal Year
2006
Total Cost
$135,967
Indirect Cost

  Institution

Name
University of Rochester
Department
Internal Medicine/Medicine
Type
Schools of Dentistry
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627

  Publications

Wang, Kening; Tomaras, Georgia D; Jegaskanda, Sinthujan et al. (2017) Monoclonal Antibodies, Derived from Humans Vaccinated with the RV144 HIV Vaccine Containing the HVEM Binding Domain of Herpes Simplex Virus (HSV) Glycoprotein D, Neutralize HSV Infection, Mediate Antibody-Dependent Cellular Cytotoxicity, and Protect Mice J Virol 91:
Himes, Jonathon E; Ho, Carrie; Nguyen, Quang N et al. (2016) Characterization of Simian Immunodeficiency Virus Variants Anatomically Compartmentalized in Plasma and Milk in Chronically Infected African Green Monkeys. J Virol 90:8795-808
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
Weaver, Jason M; Yang, Hongmei; Roumanes, David et al. (2013) Increase in IFNýý(-)IL-2(+) cells in recent human CD4 T cell responses to 2009 pandemic H1N1 influenza. PLoS One 8:e57275
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
Lamere, Mark W; Moquin, Amy; Lee, F Eun-Hyung et al. (2011) Regulation of antinucleoprotein IgG by systemic vaccination and its effect on influenza virus clearance. J Virol 85:5027-35
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
Sanz, Iñaki; Lee, F Eun-Hyung (2010) B cells as therapeutic targets in SLE. Nat Rev Rheumatol 6:326-37
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

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