Immune Mechanisms of Severe RSV Disease- T Cell and Antibody Responses

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DESCRIPTION (provided by applicant): 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.