Abstract

The immune response plays an important role in the resolution of primary influenza infection and prevention of subsequent infection in an individual. However, the relative roles of each component of the immune response in clearing infection, and the effects of interaction between 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 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 variation in viruses’ abilities to protect against subsequent infection at short inter-exposure intervals, either by delaying the second infection or inducing stochastic extinction of the second virus. It also explains the decrease in recovery time for the second infection when the two strains elicit cross-reactive cellular adaptive immune responses. To account for inter-subject as well as inter-virus variation, the model is formulated using a hierarchical framework. We will fit the model to experimental data using Markov Chain Monte Carlo methods; quantification of the model will enable a deeper understanding of the effects of potential new treatments.