RESEARCH ARTICLE Computational Characterization of Transient Strain-Transcending Immunity against

The enigmatic observation that the rapidly evolving influenza A (H3N2) virus exhibits, at any given time, a limited standing genetic diversity has been an impetus for much research. One of the first generative computational models to successfully recapitulate this pattern of consistently constrained diversity posits the existence of a strong and short-lived strain-transcending immunity. Building on that model, we explored a much broader set of scenari-os (parameterizations) of a transient strain-transcending immunity, ran long-term simula-tions of each such scenario, and assessed its plausibility with respect to a set of known or estimated influenza empirical measures. We evaluated simulated outcomes using a variety of measures, both epidemiological (annual attack rate, epidemic duration, reproductive number, and peak weekly incidence), and evolutionary (pairwise antigenic diversity, fixation rate, most recent common ancestor, and kappa, which quantifies the potential for antigenic evolution). Taking cumulative support from all these measures, we show which parameteri