Predicting the spread and impact of transmissible vaccines

预测传染性疫苗的传播和影响

• 批准号: 2314616
• 负责人: Scott Nuismer
• 金额: $ 66.45万
• 依托单位: Regents of the University of Idaho
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-10-01 至 2026-09-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2314616&HistoricalAwards=false
• 关键词: Predicting; spread; impact; transmissible; vaccines

Infectious diseases that normally thrive in wild animals occasionally make the leap into the human population. For instance, rabies virus infects and kills tens of thousands of people each year when wild animals carrying the virus bite humans and transmit the virus to them. Other viruses that occasionally leap from animals to humans are even more dangerous because they can also transmit from human to human and thus potentially seed epidemics or pandemics. Unfortunately, we do not yet have effective solutions in place to stop these infectious diseases from spilling over into the human population. Instead, our current approach to these animal diseases is reactive, and focuses on medical treatment of humans who have become infected and corralling human outbreaks before they can spread and become full blown epidemics or pandemics. A promising solution to this challenging problem is the development of wildlife vaccines that can spread themselves from one animal to the next. By self-disseminating, these vaccines magnify the spread of immunity within the wild animal population and reduce or eliminate the risk of spillover into the human population. Although multiple self-disseminating animal vaccines are being developed, we do not yet have the mathematical, statistical, and computational tools we need to critically evaluate their performance and thus make informed decisions about their possible use. Work on this project will develop these quantitative tools and enable candidate self-disseminating vaccines to be critically evaluated before they are used. In addition, this project will train first-generation college students from rural backgrounds to use mathematical and computational models to evaluate and optimize emerging biotechnologies critical to the future of the US economy. Student recruitment will be facilitated by offering competitive financial support that relieves pressure to abandon research experiences in favor of traditional employment. Finally, this project will continue development of a website that explains self-disseminating vaccines to the public, disseminates relevant research results, and examines the state of this emerging technology.Before making the decision to conduct even small-scale field trials, the likelihood that a self-disseminating vaccine will improve human health should be quantified. This requirement poses a formidable technical challenge because data on the behavior of the vaccine within the target animal population cannot be collected prior to release. This project will overcome this technical challenge using mathematical models of recombinant vector transmissible vaccines that can be parameterized using a combination of field and laboratory data. Specifically, mathematical models will be developed that integrate the age structure of the reservoir population and the explicit pattern of vaccine shedding from animals infected with vaccine. These models will take the form of a system of partial differential equations. Field data will come from trapping studies of the reservoir animal that record the age of each captured animal and whether it was infected by the vector virus used to construct the candidate vaccine. Laboratory data will describe the temporal pattern of vaccine shedding from reservoir animals experimentally infected with the vaccine. Approximate Bayesian computation will be used to parameterize the models and a stochastic simulation framework developed for predicting the outcome of a proposed vaccine release. By repeatedly simulating a vaccine release for models parameterized by drawing randomly from the posterior distribution, this framework faithfully integrates reservoir ecology, randomness in biological processes, and uncertainty in parameter estimates. The methodology developed by this project will be applied to a prototype self-disseminating vaccine for Lassa virus but will be broadly applicable to self-disseminating vaccines developing for a range of animal reservoirs.This project is jointly funded by the Population and Community Ecology (PCE) Cluster in the Division of Environmental Biology, the Established Program to Stimulate Competitive Research (EPSCoR), and the Mathematical Biology Program in the Division of Mathematical and Physical Sciences.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

通常在野生动物中猖獗的传染病偶尔也会进入人类种群。例如，每年携带狂犬病病毒的野生动物叮咬人类并将病毒传播给人类时，狂犬病病毒会感染并导致数万人死亡。其他偶尔从动物传染给人类的病毒甚至更危险，因为它们也可以在人与人之间传播，从而有可能传播流行病或大流行。不幸的是，我们还没有有效的解决方案来阻止这些传染病蔓延到人类人口中。相反，我们目前对这些动物疾病采取的方法是反应性的，重点是对已被感染的人类进行医疗治疗，并在人类疫情传播并成为全面流行或大流行之前将其围住。解决这个具有挑战性的问题的一个有希望的解决方案是开发野生动物疫苗，这种疫苗可以从一种动物传播到另一种动物。通过自我传播，这些疫苗放大了免疫在野生动物种群中的传播，减少或消除了溢出到人类种群的风险。尽管正在开发多种自我传播的动物疫苗，但我们还没有必要的数学、统计和计算工具来批判性地评估它们的性能，从而就它们可能的使用做出明智的决定。该项目的工作将开发这些量化工具，并使候选的自我传播疫苗在使用之前得到严格的评估。此外，该项目将培训来自农村背景的第一代大学生使用数学和计算模型来评估和优化对美国经济未来至关重要的新兴生物技术。招生将通过提供有竞争力的经济支持来促进，以缓解放弃研究经验、转而选择传统就业的压力。最后，该项目将继续开发一个网站，向公众解释自我传播疫苗，传播相关研究成果，并检查这项新兴技术的状况。在决定进行即使是小规模的现场试验之前，应该量化自我传播疫苗改善人类健康的可能性。这一要求带来了巨大的技术挑战，因为在发布之前无法收集有关疫苗在目标动物种群中的行为的数据。该项目将利用重组载体可传播疫苗的数学模型克服这一技术挑战，该模型可以使用现场和实验室数据的组合进行参数化。具体地说，将开发数学模型，将宿主种群的年龄结构与受疫苗感染的动物的疫苗泄漏的显式模式相结合。这些模型将采用偏微分方程组的形式。现场数据将来自对水库动物的诱捕研究，记录每一只捕获动物的年龄，以及它是否被用于构建候选疫苗的媒介病毒感染。实验室数据将描述从实验上感染疫苗的水库动物中泄漏疫苗的时间模式。将使用近似贝叶斯计算将模型参数化，并开发一个随机模拟框架来预测拟议疫苗释放的结果。通过从后验分布中随机抽取参数模型反复模拟疫苗投放，该框架忠实地集成了水库生态学、生物过程中的随机性和参数估计中的不确定性。该项目开发的方法将应用于拉萨病毒自传播疫苗的原型，但将广泛适用于为一系列动物水库开发的自传播疫苗。该项目由环境生物学部门的人口和社区生态(PCE)集群、已建立的激励竞争研究计划(EPSCoR)和数学和物理科学部门的数学生物学项目共同资助。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。