title: Impaired heterologous immunity in aged ferrets during sequential influenza A H1N1 infection.
abstract: The major burden of influenza morbidity resides within the elderly population. The challenge managing influenza-associated illness in the elderly is the decline of immune function, where mechanisms leading to immunological senescence have not been elucidated. To better represent the immune environment, we investigated clinical morbidity and immune function during sequential homologous and heterologous H1N1 influenza infection in an aged ferret model. Our findings demonstrated experimentally that aged ferrets had significant morbidity during monosubtypic heterologous 2° challenge with significant weight loss and respiratory symptoms. Furthermore, increased clinical morbidity was associated with slower and shorter hemagglutinin antibody generation and attenuated type 1 T-cell gene responses in peripheral blood. These results revealed dampened immune activation during sequential influenza infection in aged ferrets. With the presence of an aged model, dissecting clinical morbidity, viral dynamics and immune response during influenza infection will aid the development of future prophylactics such as age specific influenza vaccines.
authors.affiliation: Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada; Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Stéphane G
authors.initials: SG
authors.lastname: Paquette
authors.affiliation: Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada; Department of Immunology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Stephen S H
authors.initials: SSH
authors.lastname: Huang
authors.affiliation: Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Banner
authors.affiliation: Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Luoling
authors.initials: L
authors.lastname: Xu
authors.affiliation: Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Alberto
authors.initials: A
authors.lastname: Leόn
authors.affiliation: Immune Diagnostics & Research, Toronto Medical Discovery Tower, 101 College Street 3-913, Toronto, Ontario, Canada M5G 1L7. Electronic address: akelvin@jidc.org.
authors.forename: Alyson A
authors.initials: AA
authors.lastname: Kelvin
authors.affiliation: Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada; Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Immunology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; International Institute of Infection and Immunity, Shantou University Medical College, Guangdong, Shantou, China; Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Guangdong, China; Sezione di Microbiologia Sperimentale e Clinica, Dipartimento di Scienze Biomediche, Universita' degli Studi di Sassari, Sassari, Italy.
authors.forename: David J
authors.initials: DJ
authors.lastname: Kelvin
mesh_terms: D000367:Age Factors; D000368:Aged; D000375:Aging / Q000276:immunology*; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D004195:Disease Models, Animal; D005289:Ferrets; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D006801:Humans; D064789:Immunity, Heterologous; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology* / Q000821:virology; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines
keywords: Aging; Ferret model; Heterologous immunity; Humoral response; Immunological senescence; Influenza; Influenza A H1N1; Pandemic influenza; T-cells
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