The impact of host immune status on the within-host and population dynamics of antigenic immune escape.
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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 that the production rate of immune escape variants is driven by the accumulation of herd immunity. Overall, our results suggest that disease control strategies should be further assessed by considering the impact that increased immunity--through vaccination--has on the production of new antigenic variants.
Influenza A Virus, H3N2 Subtype
Published Version (Please cite this version)10.1098/rsif.2012.0180
Publication InfoKoelle, K; Luo, S; Mattingly, Jonathan Christopher; & Reed, Michael C (2012). The impact of host immune status on the within-host and population dynamics of antigenic immune escape. J R Soc Interface, 9(75). pp. 2603-2613. 10.1098/rsif.2012.0180. Retrieved from http://hdl.handle.net/10161/10245.
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Associate Professor in the Department of Biology
My research focuses on the ecology and evolution of infectious diseases. I use a combination of mathematical and statistical approaches to understand the processes driving the disease dynamics of pathogens. My interests include developing models to improve our understanding of how immune escape and other viral phenotypes impact the ecological dynamics of RNA viruses, and, in turn, how these ecological dynamics create selection pressures on viral pathogens. Additional interests include developing
Professor of Mathematics
Jonathan Christopher Mattingly grew up in Charlotte, NC where he attended Irwin Ave elementary and Charlotte Country Day. He graduated from the NC School of Science and Mathematics and received a BS is Applied Mathematics with a concentration in physics from Yale University. After two years abroad with a year spent at ENS Lyon studying nonlinear and statistical physics on a Rotary Fellowship, he returned to the US to attend Princeton University where he obtained a PhD in Applied and
Professor of Mathematics
Professor Reed is engaged in a large number of research projects that involve the application of mathematics to questions in physiology and medicine. He also works on questions in analysis that are stimulated by biological questions. For recent work on cell metabolism and public health, go to firstname.lastname@example.org/metabolism. Since 2003, Professor Reed has worked with Professor Fred Nijhout (Duke Biology) to use mathematical methods to understan
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