Imperfect Vaccination Can Enhance the Transmission of Highly Virulent Pathogens

“Author Summary: There is a theoretical expectation that some types of vaccines could prompt the evolution of more virulent (‘hotter’) pathogens. This idea follows from the notion that natural selection removes pathogen strains that are so ‘hot’ that they kill their hosts and, therefore, themselves. Vaccines that let the hosts survive but do not prevent the spread of the pathogen relax this selection, allowing the evolution of hotter pathogens to occur. This type of vaccine is often called a leaky vaccine. When vaccines prevent transmission, as is the case for nearly all vaccines used in humans, this type of evolution towards increased virulence is blocked. But when vaccines leak, allowing at least some pathogen transmission, they could create the ecological conditions that would allow hot strains to emerge and persist. This theory proved highly controversial when it was first proposed over a decade ago, but here we report experiments with Marek’s disease virus in poultry that show that modern commercial leaky vaccines can have precisely this effect: they allow the onward transmission of strains otherwise too lethal to persist. Thus, the use of leaky vaccines can facilitate the evolution of pathogen strains that put unvaccinated hosts at greater risk of severe disease…

Introduction: Infectious agents can rapidly evolve in response to health interventions [1]. Here, we ask whether pathogen adaptation to vaccinated hosts can result in the evolution of more virulent pathogens (defined here to mean those that cause more or faster mortality in unvaccinated hosts). 

Vaccination could prompt the evolution of more virulent pathogens in the following way. It is usually assumed that the primary force preventing the evolutionary emergence of more virulent strains is that they kill their hosts and, therefore, truncate their own infectious periods. If so, keeping hosts alive with vaccines that reduce disease but do not prevent infection, replication, and transmission (so-called “imperfect” vaccines) could allow more virulent strains to circulate. Natural selection will even favour their circulation if virulent strains have a higher transmission in the absence of host death or are better able to overcome host immunity. Thus, life-saving vaccines have the potential to increase mean disease virulence of a pathogen population (as assayed in unvaccinated hosts).”