Barriers to antigenic escape by pathogens: trade-off between reproductive rate and antigenic mutability

Robin M Bush,Steven A Frank

doi:10.1186/1471-2148-7-229

Abstract

BackgroundA single measles vaccination provides lifelong protection. No antigenic variants that escape immunity have been observed. By contrast, influenza continually evolves new antigenic variants, and the vaccine has to be updated frequently with new strains. Both measles and influenza are RNA viruses with high mutation rates, so the mutation rate alone cannot explain the differences in antigenic variability.ResultsWe develop a new hypothesis to explain antigenic stasis versus change. We first note that the antigenically static viruses tend to have high reproductive rates and to concentrate infection in children, whereas antigenically variable viruses such as influenza tend to spread more widely across age classes. We argue that, for pathogens in a naive host population that spread more rapidly in younger individuals than in older individuals, natural selection weights more heavily a rise in reproductive rate. By contrast, pathogens that spread more readily among older individuals gain more by antigenic escape, so natural selection weights more heavily antigenic mutability.ConclusionThese divergent selective pressures on reproductive rate and antigenic mutability may explain some of the observed differences between pathogens in age-class bias, reproductive rate, and antigenic variation.

Highlights

A single measles vaccination provides lifelong protection
Why do some pathogens fail to produce new antigenic variants that escape widespread immunity by the host population, whereas others readily mutate to variants that escape host immunity? This is an important question, because long-term control by vaccination depends on whether immune escape variants arise and, if they do, how quickly such variants appear
Our idea is similar to Keeling's in that both theories consider the alternative selection pressures of immediate reproductive rate versus long-term persistence

Summary

Introduction

A single measles vaccination provides lifelong protection. No antigenic variants that escape immunity have been observed. Influenza continually evolves new antigenic variants, and the vaccine has to be updated frequently with new strains. Both measles and influenza are RNA viruses with high mutation rates, so the mutation rate alone cannot explain the differences in antigenic variability. The influenza vaccine must be updated annually to track the new influenza variants that frequently arise [2]. Types A and B are the ones that mutate continuously to produce immune escape variants that cause new epidemics. Influenza type C, seems more like measles in that it does not generate variants that escape the immune memory of hosts [3]. Why do some pathogens fail to produce new antigenic variants that escape widespread immunity by the host population, whereas others readily mutate to variants that escape host immunity? This is an important question, because long-term control by vaccination depends on whether immune escape variants arise and, if they do, how quickly such variants appear

Methods

Results

Conclusion