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

美英合作：传染性疫苗对疾病生态学和病原体进化的影响：以马立克氏病病毒为例

基本信息

批准号：
10221004
负责人：
David Kennedy
金额：
$ 36.99万
依托单位：
PENNSYLVANIA STATE UNIVERSITY, THE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2025-04-30
项目状态：
未结题

项目摘要

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

疫苗接种可能是控制感染性疾病的最有效的工具之一，但是在许多情况下，包括野生动植物和农场动物疾病，后勤和经济障碍，使得对足够大的宿主疫苗接种以获得群疫苗的疫苗不切实际。可传播的疫苗定义为能够从接种疫苗到未接种疫苗的宿主传播的疫苗，通过扩大疫苗接种运动的影响，为这些挑战提供了一种潜在的解决方案。但是，可传播的疫苗并非没有风险。恢复毒力或与野生型病原体的重组可能会导致可传播的疫苗使事情变得更糟或复杂化消除努力。这项拟议的工作将首次使用经济上重要的，自然可传播的疫苗在家禽农场广泛使用中，首次量化可传播疫苗对疾病生态和进化的影响。 Marek的疾病是一种对可持续家禽生产的威胁的家禽特异性疾病，目前受到“ Rispens”疫苗的控制，这是一种现场直播的疫苗，已被广泛使用了二十年。最近的实验发现，这种疫苗能够有效地从接种疫苗到未接种疫苗的鸟类。这些结果与最近发现尚未直接接种疫苗的疫苗分离株的近期现场监测研究一致。此外，整个基因组测序的进展揭示了疫苗病毒和野生型病毒之间的重组，鉴于疫苗病毒具有高毒性形式的致癌性MEQ基因。总之，这些观察结果表明，利斯彭疫苗是一种可传播的疫苗，能够发展并有可能促进Wildtype Marek病毒的不良进化。我们的主要目的是量化可传染性疫苗使用的后果。具体而言，我们将：1）开发一种可传播疫苗接种的通用模型，以鉴定关键知识差距，2）表征疫苗传播及其对野生型病毒传播的影响，3）表征Wildtype病毒和疫苗病毒的遗传演化，4）模型，模型