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The evolutionary dynamics of receptor binding avidity in influenza A: a mathematical model for a new antigenic drift hypothesis.

Abstract

The most salient feature of influenza evolution in humans is its antigenic drift. This process is characterized by structural changes in the virus's B-cell epitopes and ultimately results in the ability of the virus to evade immune recognition and thereby reinfect previously infected hosts. Until recently, amino acid substitutions in epitope regions of the viral haemagglutinin were thought to be positively selected for their ability to reduce antibody binding and therefore were thought to be responsible for driving antigenic drift. However, a recent hypothesis put forward by Hensley and co-workers posits that cellular receptor binding avidity is the dominant phenotype under selection, with antigenic drift being a side effect of these binding avidity changes. Here, we present a mathematical formulation of this new antigenic drift model and use it to show how rates of antigenic drift depend on epidemiological parameters. We further use the model to evaluate how two different vaccination strategies can impact antigenic drift rates and ultimately disease incidence levels. Finally, we discuss the assumptions present in the model formulation, predictions of the model, and future work that needs to be done to determine the consistency of this hypothesis with known patterns of influenza's genetic and antigenic evolution.

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