A Mathematical Theory of Transmissible Vaccines

每年，数百万人因从野生或野生动物中溢出的病原体而受到伤害或死亡。 家畜水库。减少溢出威胁的一种新方法是消除 使用可传播的疫苗，从动物传播到 在它们离开时提供对病原体的免疫力。可传播疫苗可减少 动物宿主内的病原体控制所需的疫苗接种工作，并允许疫苗 深入偏远的水库栖息地，那里不可能直接接种疫苗。提起这个 革命性的想法需要我们同时设计疫苗：1） 有效地在动物之间传播，2）刺激对靶标的强大免疫应答 病原体，和3）在进化压力面前保持其完整性。该项目将 开发数学模型，预测疫苗的这些特征是如何从 疫苗复制和动物免疫反应之间的相互作用。这些模型将在 使用原型传染性疫苗的实验室研究进行参数化和验证， 使用鼠巨细胞病毒（MCMV）作为载体骨架。我们把MCMV作为一种载体 因为它具有高度的种特异性，能够重复感染，并为疫苗提供了模型， 在鼠类啮齿动物中的发展，作为广泛的 人类病原体这些模型将使用免疫耗竭小鼠的实验进行验证 这挑战了他们解释模式和过程的能力。在这个项目上的工作资本化 数学建模、病毒进化和 鼠巨细胞病毒

Each year, millions of people are harmed or killed by pathogens that spill over from wild or domestic animal reservoirs. A new approach to reducing the threat of spillover is to eliminate the pathogen from its animal reservoir using transmissible vaccines that move from animal to animal providing immunity to the pathogen as they go. Transmissible vaccines reduce the vaccination effort required for pathogen control within animal reservoirs and allow the vaccine to penetrate remote reservoir habitats where direct vaccination is impossible. Bringing this revolutionary idea to fruition requires that we engineer vaccines that simultaneously: 1) transmit efficiently from animal to animal, 2) stimulate a robust immune response to the target pathogen, and 3) maintain their integrity in the face of evolutionary pressures. This project will develop mathematical models that predict how these traits of the vaccine emerge from the interplay between vaccine replication and the animal’s immune response. These models will be parameterized and validated using laboratory studies of prototype transmissible vaccines that use murine cytomegalovirus (MCMV) as a vector backbone. We focus on MCMV as a vector because it is highly species specific, capable of superinfection, and provides a model for vaccine development across murine rodents that serve as important reservoirs for a wide range of human pathogens. The models will be validated using experiments with immune depleted mice that challenge their ability to explain both pattern and process. Work on this project capitalizes on an existing collaboration between experts in mathematical modeling, viral evolution, and murine cytomegalovirus.