Impaired heterologous immunity in aged ferrets during sequential influenza A H1N1 infection

- The major burden of influenza morbidity resides within the elderly.
- We developed an aged ferret model to study influenza and the aged immune system.
- We found sequential H1N1 infection caused significant morbidity in aged ferrets.
- Aged ferrets had reduced HA antibody generation and type 1 T-cell responses.
- The aged ferret model will aid the development of age specific therapeutics.

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.