Computational investigations of the immune response to repeated influenza infections and vaccinations

Previous studies have shown that repeated influenza vaccination can enhance susceptibility to subsequent infection with a drifted influenza virus strain. This paper seeks to further understanding of the interactions between influenza viruses and specific immune cells that accompany this phenomenon. The paper argues that repeated vaccination increases susceptibility to infection only in the context of a residual immunity induced by prior vaccination or infection. The results of computational analysis indicate that this is a dynamic consequence of interactions between vaccines, influenza viruses and specific immune cells. In particular, mathematical modelling was used to show that in the presence of residual immunity conferred by a vaccine administered in Canada in the 2013–2014 influenza season, the 2014–2015 season vaccine enhanced susceptibility to infection. Such infection enhancement occurs when the 2014–2015 vaccine boosts suppressive T-regulatory cells induced by the 2013–2014 vaccine, decreasing the strength of antibody responses to the infecting strain. Overall, the study suggests probable characteristics of infecting viruses and vaccines that make repeated influenza infections and vaccinations detrimental.