US-UK Collab: The consequences of transmissible vaccines on disease ecology and pathogen evolution: Marek's disease virus as a case study

Decades of evidence from Human and Veterinary Medicine has undoubtedly demonstrated the important role of vaccination in the control of infectious diseases. Transmissible vaccines, or self-disseminating vaccines, are vaccines capable of transmitting between individuals. Such vaccines, by nature of their ability to disseminate to hosts that were themselves not directly vaccinated, show substantial promise for interventions in wildlife populations, because each administered vaccine has the potential to reach otherwise inaccessible potential hosts. They may also be useful on farmed populations such as fish or chickens where vaccinating every animal will be difficult. Moreover, such vaccines might be capable of persisting in the animal population over time, reducing the urgency to vaccinate every time populations turn over, such as during reproductive seasons or between farm cohorts.

However, the effects of such transmissible vaccines on the virus dynamics and evolution of pathogens, as well as potential recombination have not been examined. This project is developed from the findings of the previous EEID grant, where we found that the more efficient Rispens vaccine against Marek's disease is transmissible between birds. So the concept of the investigation is to examine more about the transmission dynamics and protection of transmissible vaccines that spread between birds. As part of the project, we will investigate whether transmissible vaccine can also drive virus evolution to greater virulence and whether such vaccines can contribute to recombination. The key question we will try to answer using controlled experiments in chickens as to whether transmissible vaccines will make things better or worse. So far a number of theoretical studies on transmissible vaccines have not given conclusive answers. We believe that the efficient transmissible vaccine model in Marek's disease will be valuable to examine how the theory and empirical data can be combined to ask what the overall consequences of transmissible vaccines are on disease ecology and evolution.

Vaccination can be one of the most efficient and effective tools for controlling the burden of infectious diseases, but in many settings, such as for wildlife diseases or farm animal diseases, logistical or economic hurdles make it impractical to vaccinate large enough fractions of hosts to achieve herd immunity. Transmissible vaccines, defined as vaccines capable of disseminating from vaccinated to non-vaccinated hosts, offer one potential solution to these challenges by amplifying the impact of vaccination campaigns. However, transmissible vaccines are not without risk. Reversion to virulence or recombination with wildtype pathogens could cause transmissible vaccines to make matters worse or complicate elimination efforts. This proposed work will for the first time quantify the effects of transmissible vaccines on disease ecology and evolution using the example of an economically important, naturally transmissible vaccine currently in widespread use on poultry farms.
Marek's disease, a poultry-specific disease that is a threat to sustainable chicken and egg farming, is currently controlled by the "Rispens" vaccine, a live, attenuated vaccine that has been widely used for two decades. Recent experiments have found that this vaccine is capable of efficiently transmitting from vaccinated to non-vaccinated chickens. Our primary objective is to use this study system to quantify the consequences of transmissible vaccine use in controlled experimental conditions: Specifically, we will:
1) Develop a general model of transmissible vaccination to identify key knowledge gaps
2) Characterize vaccine transmission and its impact on wildtype virus transmission
3) Characterize the genetic evolution of wildtype virus and vaccine virus
4) Model the overall impact of Rispens vaccination on Marek's disease virus and its vaccine
This study will provide the first empirical estimate of how well a transmissible vaccine disseminates in the population for inducing protection.