COLLABORATIVE RESEARCH: A MATHEMATICAL THEORY OF TRANSMISSIBLE VACCINES

合作研究：传播疫苗的数学理论

• 批准号: 9247312
• 负责人: SCOTT L NUISMER
• 金额: $ 25.14万
• 依托单位: UNIVERSITY OF IDAHO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9247312
• 关键词: Accounting; Archives; Attenuated Vaccines; Bacteria; Bacteriophages; Benign; Biological Models; Biology; Collaborations; Communicable Diseases; Cowpox; Development; Disease; Ecology; Engineering; Epidemiologic Studies; Epidemiology; Evolution; Foundations; Genes; Genetic; Genetic Engineering; HIV; Health; Herd Immunity; Human; Human poliovirus; Immunity; Individual; Infectious Agent; Invaded; Laboratories; Life; Mathematics; Methods; Modeling; Modification; Molecular Biology; Patients; Poliomyelitis; Population; Research; Risk; Science; Smallpox; System; Target Populations; Testing; Time; Vaccinated; Vaccination; Vaccine Production; Vaccines; Viral; Viral Vaccines; Virulence; Virus; Wild Animals; Work; World Health; base; fictional works; laboratory experiment; mathematical model; mathematical theory; novel; programs; simulation; sound; success; theories; vaccine delivery; vaccine evaluation

Viral vaccines have had remarkable and long-lasting impacts on human health, resulting in the world wide eradication of smallpox, the elimination of polio within much of the developed world, and the effective control of many other diseases. Although great strides have been made in the development and production of vaccines since Edward Jenner's first vaccinations with cowpox in the early 1800's, little has changed in the way vaccines are delivered. Even today, virtually every vaccine must be given directly to the patient. Recent advances in molecular biology suggest that the centuries-old method of individual-based vaccine delivery could be on the cusp of a major revolution. Specifically, genetic engineering brings to life the possibility of a "transmissible vaccine." Rather than directly vaccinating every individual within a population, a transmissible vaccine would allow large swaths of the population to be vaccinated effortlessly by releasing an infectious agent that is genetically engineered to be benign yet infectious. In fact, some existing vaccines are transmissible to a limited extent, and transmissible vaccines have already been developed and deployed in wild animal populations. Remarkably enough, however, no theory exists to guide the safe and effective use of this revolutionary new type of vaccine. We will develop a mathematical framework for understanding the ecology and evolution of transmissible vaccines, and test the emerging mathematical results using an experimental viral system. Epidemiological efficacy will be assessed by calculating the gains in disease protection conferred by a transmissible vaccine relative to a traditional vaccine. Evolutionary robustness will be explored using models that predict the rate at which a genetically engineered vaccine will lose its efficacy or increase its virulence. In both cases, models will be analyzed using a combination of direct and asymptotic solutions, approximations, numerical solutions, and individual-based simulations. Key mathematical results will be tested experimentally using interactions between bacteria and viruses that infect them.

病毒疫苗对人类健康产生了显着和持久的影响，导致了全球天花的根除，在大部分发达国家中消除了脊髓灰质炎以及对许多其他疾病的有效控制。尽管自爱德华·詹纳（Edward Jenner）在1800年代初期首次使用cowpox接种疫苗以来，在疫苗的开发和生产方面取得了长足的进步，但接种方式的交付方式几乎没有改变。即使在今天，几乎每种疫苗都必须直接给予患者。分子生物学的最新进展表明，基于个体的疫苗输送的几个世纪历史的方法可能是主要革命的风口浪尖。具体而言，基因工程使“可传染性疫苗”的可能性增强。可传染性的疫苗不直接接种人群中的每个人，而是通过释放一种经过基因设计为良性但感染性的传染剂来轻松接种大量人群。实际上，某些现有的疫苗在有限的程度上是可以传播的，并且已经在野生动物种群中开发和部署了可传播的疫苗。然而，值得注意的是，没有任何理论来指导这种革命性的新型疫苗的安全有效使用。我们将开发一个数学框架，以理解可传染性疫苗的生态和演变，并使用实验性病毒系统测试新兴的数学结果。流行病学疗效将通过计算可传播疫苗相对于传统疫苗赋予的疾病保护的收益来评估。将使用模型来探索进化鲁棒性，以预测基因工程疫苗将失去疗效或增加其毒力的速率。在这两种情况下，将使用直接和渐近解决方案，近似值，数值和基于个体的模拟的组合分析模型。关键的数学结果将通过细菌与感染它们的病毒之间的相互作用进行实验测试。