YY-EEID US-UK Collab: Combined influence of imperfect vaccines, host genetics, and non-genetic drivers on virus transmission and virulence evolution

摘要(最多4000个字符)为了维持人类和动物的健康，了解像病毒这样的病原体是如何传播和进化到更高的毒力是极其重要的。正是这种知识使人们能够采用有效和可持续的控制战略。因此，有必要收集、收集和分析高度准确的数据集，以确定疾病控制方法的短期和长期有效性，这些方法包括生物安全、抗病基因选择和广泛接种疫苗。在这个项目中，一个国际跨学科团队调查了这些方法对两种禽类致病病毒--马立克氏病病毒(MDV)和传染性支气管炎病毒(IBV)--传播和进化的影响，这两种病毒主要由不完善的疫苗控制。有人认为，不完善的疫苗，如MDV和IBV的疫苗，或宿主的遗传抗性，可能会改变病原体传播和毒力之间的选择平衡，因为它允许以更低的成本传播更多不同但仍具有毒力的毒株。然而，这些假说还没有得到证实，而且缺乏预测框架来确定宿主和病毒遗传学以及疫苗接种对病毒传播和进化到更高毒力的联合影响。为了解决这些知识差距，设计了一系列传播实验，在高度受控的条件下利用7000多只鸟类的独特资源和数据。总而言之，这项研究的主要目标是收集信息丰富的高分辨率经验数据，并使用这些数据来构建下一代数据知情的病毒传播和进化动力学模型，该模型是疫苗接种状态、宿主遗传学和/或病毒变异率的函数。我们还将解决基因组变异和进化的重要和可能相互依赖的问题，以提高活体毒力。除了这项研究的纯科学价值外，我们还努力将该项目提升到高度的实用意义。这需要一个完整的系统方法，同时考虑到疾病传播和毒力演变的更广泛的社会经济和政治驱动因素。我们将结合社会经济研究和数学模型来确定在撒哈拉以南非洲减缓MD传播和MDV毒力进化的策略，那里的家禽生产目前正在经历商业生产的急剧增长，类似于20世纪60年代在美国观察到的情况。我们提出以下目标，以实现科学上的卓越和获得更广泛的影响：1.确定不完善的疫苗、宿主遗传学和病毒突变率对传播和进化到更高毒力的影响。验证与病毒毒力增强和病毒逃避免疫监视能力相关的病毒基因组多态。建立数据知情的进化-流行病学模拟模型，以制定控制MDD的生态、进化和经济负担的策略。通过培训、讲习班、在线视频、研讨会和各种参与活动，向家禽生产者和公众传播关于MDV和IBV的信息以及疫苗接种的影响

Summary (up to 4000 characters)To maintain human and animal health, it is extremely important to understand how pathogens like viruses are transmitted and evolve to higher virulence. It is this knowledge that enables employment of effective and sustainable control strategies. Thus, it is necessary to collect, assemble, and analyse highly accurate datasets to determine the short- and long-term effectiveness of disease control approaches, that include biosecurity, genetic selection for disease resistance, and widespread vaccination. In this project, an international, interdisciplinary team investigates the impact of these approaches on the spread and evolution of two avian pathogenic viruses - Marek's disease virus (MDV) and infectious bronchitis virus (IBV) - both of which are primarily controlled by imperfect vaccines. It has been argued that imperfect vaccines like those to MDV and IBV, or host genetic resistance may alter the balance of selection between pathogen transmission and virulence by allowing a few more divergent but still virulent strains to be transmitted at reduced cost. However, these hypotheses have not been proven, and predictive frameworks are lacking for determining the combined influence of host and viral genetics, as well as vaccination on viral transmission and evolution to increased virulence. To address these knowledge gaps, a series of transmission experiments have been designed that utilize unique resources and data from 7,000+ birds under highly controlled conditions. In summary, the primary goal of this research is to collect informative, high-resolution empirical data and use these to build the next generation of data-informed mathematical models of virus transmission and evolutionary dynamics as a function of vaccination status, host genetics, and/or viral mutation rates. We will also address the important and possibly interdependent questions of genome variability and evolution towards increased virulence in vivo.Besides the pure scientific merit of this research, we also strive towards lifting the project to high practical relevance. This requires a whole systems approach that also considers the broader socio-economic and political drivers of disease spread and virulence evolution. We will combine socio-economic studies with mathematical modelling to identify strategies for mitigating MD spread and MDV virulence evolution in sub-Saharan Africa, where poultry production is currently undergoing drastic increases in commercial production, similar to what was observed in the US in the 1960s.We propose the following objectives to achieve scientific excellence and attain broader impact:1. Determine the influence of imperfect vaccines, host genetics, and viral mutation rate on transmission and evolution to higher virulence.2. Validate viral genome polymorphisms associated with increased virulence and the ability of the virus to escape immune surveillance.3. Build data-informed evolutionary-epidemiological simulation models to develop strategies to control the ecology, evolution and economic burden of MD.4. Disseminate information on MDV and IBV, and the impact of vaccination to poultry producers and the public through training, workshops, online videos, seminars, and various engagement activities