Schematic illustration of the simulation sequence. SubramanianRahul L. GrahamAndrea T. GrenfellBryan ArinaminpathyNimalan 2016 <p>As described in the Methods, the simulation is initiated by a pandemic in a naïve population. In subsequent seasons we assume that strain selection happens during the interepidemic period (annotated by a virus in the Figure, and corresponding to <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1005204#pcbi.1005204.g001" target="_blank">Fig 1B</a>). This leads to a loss of strain-specific immunity due to antigenic drift, and accompanies a loss of immunity through population turnover, as well as through decay of cross-protective immunity. We assume that routine vaccination, whether conventional or universal, occurs just prior to each seasonal epidemic (annotated by a syringe in the Figure). The epidemic that follows is governed by the <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1005204#pcbi.1005204.e001" target="_blank">eq (1)</a> in the main text, leading to a gain of immunity in the population (corresponding to <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1005204#pcbi.1005204.g001" target="_blank">Fig 1A</a>)). We iterate through seasons in this way, ultimately reporting the ‘seasonal epidemic size’ as the mean epidemic size between seasons 5 and 24, and the ‘pace of antigenic evolution’ as the mean distance between successive strains during this period. Finally, we simulate a pandemic in year 25, assuming a virus to which cross-protective immunity, and not strain-matched immunity, is effective.</p>