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Imperfect vaccines and the evolution of pathogen virulence

Abstract

Vaccines rarely provide full protection from disease. Nevertheless, partially effective (imperfect) vaccines may be used to protect both individuals and whole populations1,2,3. We studied the potential impact of different types of imperfect vaccines on the evolution of pathogen virulence (induced host mortality) and the consequences for public health. Here we show that vaccines designed to reduce pathogen growth rate and/or toxicity diminish selection against virulent pathogens. The subsequent evolution leads to higher levels of intrinsic virulence and hence to more severe disease in unvaccinated individuals. This evolution can erode any population-wide benefits such that overall mortality rates are unaffected, or even increase, with the level of vaccination coverage. In contrast, infection-blocking vaccines induce no such effects, and can even select for lower virulence. These findings have policy implications for the development and use of vaccines that are not expected to provide full immunity, such as candidate vaccines for malaria4.

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Figure 1: Schematic representation of the action of different types of host resistance at different stages of the pathogen's life cycle.
Figure 2: Evolutionary and epidemiological consequences of using different types of vaccines.
Figure 3: Predicted effects of anti-malaria vaccination coverage on virulence.

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Acknowledgements

We thank M. van Baalen, R. Carter, D. Ebert, V. Jansen, T. Little, Y. Michalakis, F. Rousset, and S. West for discussions, and the Leverhulme Trust, BBSRC and the Wellcome Trust for support.

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Correspondence to Sylvain Gandon.

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Supplementary information

Supplementary methods and analysis (DOC 343 kb)

Figure 4

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Schematic representation of the epidemiological model described in equation (5).

Figure 5

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Invasion dynamics of a virulence mutant after the start of vaccination campaign using an anti-growth rate vaccine (r2=0.8 and ri=r3=r4=0) with a vaccination coverage of 90%. In this simulation the virulence of the resident strain is the ES virulence in the absence of vaccination (αN=0.0153). We present the invasion dynamics of invasion of a mutant with virulence equal to the ES level after vaccination (αN=0.0418). At the start of the vaccination campaign we assumed that the mutant was at an initial frequency of 1% (full line), 0.1% (dashed line) or 0.01% (dotted line). We further assumed that its distribution among naïve and immune hosts was identical to the distribution of the resident strain before vaccination.

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Gandon, S., Mackinnon, M., Nee, S. et al. Imperfect vaccines and the evolution of pathogen virulence. Nature 414, 751–756 (2001). https://doi.org/10.1038/414751a

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