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

Public Health Relevance

Transmissible vaccines are being widely considered to control zoonotic diseases in animal populations, including Ebola, Marburg, Sin Nombre hantavirus, and rabies. However, before transmissible vaccines are introduced, the benefits and risks must be considered. This study will provide the first empirical estimate of how well a transmissible vaccine spreads, and it will determine whether adverse evolution has occurred due to the widespread use of a transmissible vaccine, or if not, whether it is likely to occur.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM140459-01
Application #
10133216
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Janes, Daniel E
Project Start
2020-08-01
Project End
2025-04-30
Budget Start
2020-08-01
Budget End
2021-04-30
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
003403953
City
University Park
State
PA
Country
United States
Zip Code
16802