Seasonal influenza leads to an annual average of over 200,000 cases of hospitalizations and 36,000 deaths in the United States alone. Of all influenza-associated deaths, 90% occur in adults over the age of 65 years. Current approaches to vaccination of human elderly against seasonal influenza are inadequate. The task of developing an improved influenza intervention for the elderly is complicated by the absence of an appropriate animal model of influenza disease in the aged. Infection with unadapted seasonal influenza viruses is easily achieved in the cotton rat S.hispidus, an animal with high translational value for research on respiratory viruses. Aging in cotton rats significantly alters pathogenesis of respiratory viral infections, with seasonal influenza infection causing a more severe disease in the aged cotton rats. Efficacy of human influenza vaccines has been demonstrated in younger cotton rats using trivalent inactivated vaccine FluLaval. In this work, we will validate the aged cotton rat model of human seasonal influenza vaccines by demonstrating age-related decline in immunogenicity of both trivalent inactivated (FluLaval, GSK) and live attenuated (FluMist, MedImmune) vaccines. Vaccine efficacy will be evaluated against immunologic parameters reported to characterize aging in humans and expanded to define biomarkers of severe seasonal influenza disease in human elderly and their modification by various vaccination regimes. Validation of this platform would yield a valuable translational model that can be used to improve existing methods of seasonal influenza vaccination of human elderly and to devise novel effective vaccines.
Disease caused by seasonal influenza carries a deadly toll on human elderly. Current approaches to vaccination of elderly against influenza are not effective and cannot be improved in the absence of an appropriate animal model. The cotton rat S.hispidus is susceptible to infection with unadapted influenza viruses and shows age-related alterations in influenza pathogenesis leading to a more severe disease. In this proposal we will use the aged cotton rats to recapitulate deficiencies of trivalent inactivated and live attenuated influenza vaccines as reported for human elderly. Creation of a translational animal model of influenza vaccines for elderly would facilitate design of a more effective vaccination approaches and reduce disease burden in this fast-growing population.
