The impact of host immune status on the within-host and population dynamics of antigenic immune escape.

Journal of the Royal Society, Interface
Shishi LuoKatia Koelle

Abstract

Antigenically evolving pathogens such as influenza viruses are difficult to control owing to their ability to evade host immunity by producing immune escape variants. Experimental studies have repeatedly demonstrated that viral immune escape variants emerge more often from immunized hosts than from naive hosts. This empirical relationship between host immune status and within-host immune escape is not fully understood theoretically, nor has its impact on antigenic evolution at the population level been evaluated. Here, we show that this relationship can be understood as a trade-off between the probability that a new antigenic variant is produced and the level of viraemia it reaches within a host. Scaling up this intra-host level trade-off to a simple population level model, we obtain a distribution for variant persistence times that is consistent with influenza A/H3N2 antigenic variant data. At the within-host level, our results show that target cell limitation, or a functional equivalent, provides a parsimonious explanation for how host immune status drives the generation of immune escape mutants. At the population level, our analysis also offers an alternative explanation for the observed tempo of antigenic evolution, namely ...Continue Reading

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Citations

Apr 24, 2013·Journal of Theoretical Biology·Lisa N MurilloAlan S Perelson
Sep 25, 2015·BMC Biology·H Frederik NijhoutMichael C Reed
Aug 1, 2014·PLoS Computational Biology·Christopher J R IllingworthVille Mustonen
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