Journal
VIROLOGY
Volume 464, Issue -, Pages 177-183Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2014.07.013
Keywords
Influenza A H1N1; Pandemic influenza; Influenza; Heterologous immunity; Aging; Immunological senescence; Ferret model; Humoral response; T-cells
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Funding
- Li Ka-Shing Foundation of Canada
- Immune Diagnostics & Research, Shantou University Medical College
- NIH [UO1A1111598, 0038951(123721-3)]
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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 degrees 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. (C) 2014 The Authors. Published by Elsevier Inc.
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