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

Luo, Shishi

Reed, Michael

Mattingly, Jonathan C

Koelle, Katia

England

2015-07-04T21:24:32Z

2012-10-07

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.

http://www.ncbi.nlm.nih.gov/pubmed/22572027

rsif.2012.0180

1742-5662

https://hdl.handle.net/10161/10245

eng

The Royal Society

J R Soc Interface

10.1098/rsif.2012.0180

Antigenic Variation

Humans

Immune Evasion

Immunity, Innate

Influenza A Virus, H3N2 Subtype

Influenza, Human

Models, Immunological

Population Dynamics

Viral Load

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

Journal article

Mattingly, Jonathan C|0000-0002-1819-729X

http://www.ncbi.nlm.nih.gov/pubmed/22572027

2603

2613

75

Biology

Duke

Global Health Institute

Institutes and Provost's Academic Units

Mathematics

Statistical Science

Trinity College of Arts & Sciences

University Institutes and Centers

Published

9