Understanding Emerging Zoonotic Respiratory Viruses

The objective of the work presented in this thesis was to improve understanding of, and response to, emerging zoonotic respiratory viruses. To this end, various animal models were employed to represent respiratory viral infections in humans. The introduction serves to provide a background on the currently available animal models and (potential) vaccine strategies for human influenza and coronavirus infections.

For the work presented in this thesis, animal models were used in three distinct ways, underlining that the choice of animal model depends largely on the research question. In Chapter 2-4 a new isogenic guinea pig model was developed that provides unique features compared to established influenza virus models. The baseline parameters of influenza infection in this model were assessed to determine its suitability for use to simultaneously study transmission and cell mediated immunity to influenza infections. In Chapter 5, an established model was used to test a novel intervention strategy for an emerging influenza subtype. We showed that the modified vaccinia ankara (MVA)- H7 vaccine is effective against the newly emerging influenza A/H7N9 virus in the ferret model and that it satisfies one of the main aims of the novel influenza vaccines: rapid availability. Finally in Chapter 6, a new model was explored to gain understanding of the pathogenesis of a recently emerged coronavirus. Cynomolgous macaques were used to study underlying mechanisms that appear to restrict MERS-CoV replication in some hosts and data was compared to two other coronaviruses SARS-CoV and NL63-CoV.

In the summarizing discussion (Chapter 7), further attention is paid to the parallels and differences between coronaviruses and influenza viruses, what questions remain to be answered and how we may hope to answer them.