Rapid mutation of the influenza virus presents a challenge for vaccination, as current vaccines only protect against a subset of virus strains. Next-generation vaccines aim to stimulate different components of the immune response to confer immunity against a broad spectrum of viral strains. However, the relative roles of each component of the immune response in clearing infection, and the effects of interaction between immune response components, are not well quantified. 

We have constructed a model of the immune response to influenza based on data from viral interference experiments, where ferrets were exposed to two influenza strains within a short time period. The data shows that a primary infection can protect against subsequent infection with a different influenza strain, and exhibits a hierarchy in viruses' abilities to protect against subsequent infection. The changes in viral kinetics of the second virus due to the first virus depend on the strains used as well as the interval between exposures, enabling inference of the timing of innate and adaptive immune response components and the role of cross-reactivity in resolving infection. Our model provides a mechanistic explanation for the observed hierarchy of viruses' abilities to protect against subsequent infection at short inter-exposure intervals, and for the shortening of the second infection when the two strains elicit cross-reactive cellular adaptive immune responses. An experimentally-validated model of the immune response to influenza will enable a deeper understanding of the effects of potential new treatments.

Ada Yan is a PhD student at the School of Mathematics and Statistics at the University of Melbourne. Her PhD centers on modelling the host immune response to influenza using data obtained from novel experiments conducted by collaborators at the WHO Collaborating Centre for Reference and Research on Influenza. Ada's visit to the Fields Institute is funded by the Victoria Fellowship; during her study trip, she will work with collaborators in Canada and the UK to model the immune response to influenza in immunocompromised individuals.