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

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Vaccination can be one of the most efficient and effective tools for controlling infectious diseases, but in many settings, including wildlife and farm animal diseases, logistical and 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 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 poultry production, 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 birds. These results are consistent with recent field surveillance studies that have found vaccine isolates in cohorts that have not been directly vaccinated. In addition, advances in whole genome sequencing have revealed recombination between the vaccine virus and the wildtype virus, which is concerning given that the vaccine virus harbors highly virulent forms of the oncogenic meq gene. Together, these observations demonstrate that the Rispens vaccine is a transmissible vaccine capable of evolving and potentially facilitating adverse evolution of wildtype Marek's disease virus. Our primary objective is to quantify the consequences of transmissible vaccine use. 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