Delay of innate immune responses following influenza B virus infection affects the development of a robust antibody response in ferrets

The ferret is the primary animal model for human influenza research. Using a ferret model, we studied the differences in both innate and adaptive immune responses following infection with influenza A and B viruses (IAV and IBV). Antibodies generated following infection of ferrets is used for surveillance assays to detect antigenic drift and cross-reactivity with vaccine viruses and circulating influenza strains. IAV infection of ferrets to generate these reagents resulted in a strong antibody response, but IBV infection generated weak antibody responses. In this study using influenza-infected ferrets, we found that IAV resulted in an early activation of the interferon (IFN) and pro-inflammatory response, whereas IBV showed a delay and reduction in these responses. Serum levels of IFNs and other cytokines or chemokines were much higher in ferrets following IAV infection. These reduced innate responses were reflected the subsequent delayed and reduced antibody responses to IBV in the sera. These findings may help in understanding low antibody responses in humans following influenza B vaccination and infection and may warrant the use of innate immunomodulators to overcome these weak responses.