Our influenza research program focuses on characterizing virus-host interactions to identify correlates of protection as a starting point for the development of rationally designed vaccines. Towards this, we are generating recombinant viruses with specific modifications in their coding or non-coding regions. After a detailed characterization in vitro, the pathogenesis and host response profile associated with these viruses are then evaluated in different animal models. Results obtained are integrated in the design of new vaccine candidates or therapeutic approaches. Most of these studies are done in ferrets, since they are naturally susceptible to human isolates, and they develop a disease similar to that seen in humans.
To further develop this animal model, we are continuously generating new reagents and assays to improve the assessment of the host response in ferrets. We are also increasingly exploring the potential of telemetry and classical as well as novel in vivo imaging technologies to objectively assess the clinical disease severity. Using immunological assays developed in the laboratory, we have shown that the early cytokine response of ferrets reproduces results from human clinical studies, demonstrating the value of this model for host response studies.
At this time, we are investigating the mechanisms underlying the observed protection conferred by prior influenza infection against re-infection with different subtypes. I a separate project, we are modulating cellular proteins involved in the influenza life cycle to assess their potential in reducing disease severity.