A Mathematical Theory of Transmissible Vaccines

传播疫苗的数学理论

• 批准号: 10583400
• 负责人: SCOTT L NUISMER
• 金额: $ 36.71万
• 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 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10583400
• 关键词: 2019-nCoV; Animals; Automobile Driving; Brucella; Chronic; Collaborations; Combined Vaccines; Cytomegalovirus; Development; Disease; Domestic Animals; Ebola; Effectiveness; Engineering; Epidemic; Evolution; Face; Foundations; Genetic Engineering; Growth; Habitats; Human; Immune; Immune response; Immunity; Immunization Programs; In Vitro; Individual; Infection; Influenza; Influenza A Virus, H1N1 Subtype; Injections; Laboratory Study; Lassa virus; Methodology; Modeling; Murid herpesvirus 1; Mus; Pattern; Penetration; Performance; Persons; Play; Population; Prevention; Procedures; Process; Property; Rabies; Rodent; Role; Severe Acute Respiratory Syndrome; Source; Technology; Transgenes; Vaccinated; Vaccination; Vaccine Design; Vaccines; Validation; Vertebral column; Viral; Virus; Wild Animals; Work; Zoonoses; cost; design; experimental study; human disease; human pathogen; immunogenic; immunogenicity; in vivo; mathematical model; mathematical theory; new technology; novel; novel strategies; pandemic disease; pathogen; pathogen spillover; predictive modeling; pressure; prevent; programs; prototype; superinfection; trait; transmission process; vaccine candidate; vaccine development; vaccine distribution; vaccine evaluation; vector

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.

每年，数以百万计的病原体伤害或杀害，这些病原体从野外溢出或 家养动物水库。减少Spilover威胁的一种新方法是消除 使用可传播的疫苗从动物转移到动物的动物储层的病原体 动物随着病原体提供免疫力。可传播的疫苗减少了 动物储层内病原体控制所需的疫苗努力并允许疫苗 要穿透不可能直接疫苗接种的远程依赖器胎儿。带这个 流动的革命性想法要求我们设计简单的疫苗：1） 有效地从动物传输到动物，2）刺激对靶标的强大的免疫反应 病原体和3）在面对进化压力的情况下保持其完整性。这个项目将 开发数学模型，以预测疫苗的这些特征如何从 疫苗复制与动物的免疫反应之间的相互作用。这些模型将是 使用针对传播疫苗的原型实验室研究进行参数化和验证 使用鼠巨细胞病毒（MCMV）作为矢量骨架。我们专注于MCMV作为向量 因为它是高度特异的，能够超级感染，并为疫苗提供了模型 间鼠啮齿动物的开发，这些啮齿动物是重要的储层 人类病原体。这些模型将使用免疫耗尽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。研究该项目的资本化 关于数学建模，病毒演化和 鼠巨细胞病毒。

项目成果

Evading resistance to gene drives.

• DOI: 10.1093/genetics/iyaa040
• 发表时间: 2021-02-09
• 期刊: Genetics
• 影响因子: 3.3
• 作者: Gomulkiewicz R;Thies ML;Bull JJ
• 通讯作者: Bull JJ

When to vaccinate a fluctuating wildlife population: Is timing everything?

何时为波动的野生动物种群接种疫苗：时机就是一切吗？

• DOI: 10.1111/1365-2664.13539
• 发表时间: 2020
• 期刊: The Journal of applied ecology
• 作者: Schreiner,CourtneyL;Nuismer,ScottL;Basinski,AndrewJ
• 通讯作者: Basinski,AndrewJ

Suppressing evolution in genetically engineered systems through repeated supplementation.

• DOI: 10.1111/eva.13119
• 发表时间: 2021-03
• 期刊: Evolutionary applications
• 影响因子: 4.1
• 作者: Layman NC;Tuschhoff BM;Basinski AJ;Remien CH;Bull JJ;Nuismer SL
• 通讯作者: Nuismer SL

Predicting the fine-scale spatial distribution of zoonotic reservoirs using computer vision.

使用计算机视觉预测人畜共患病水库的精细空间分布。

• DOI: 10.1111/ele.14307
• 发表时间: 2023
• 期刊: Ecology letters
• 影响因子: 8.8
• 作者: Layman,NathanC;Basinski,AndrewJ;Zhang,Boyu;Eskew,EvanA;Bird,BrianH;Ghersi,BrunoM;Bangura,James;Fichet-Calvet,Elisabeth;Remien,ChristopherH;Vandi,Mohamed;Bah,Mohamed;Nuismer,ScottL
• 通讯作者: Nuismer,ScottL

Methods for measuring the evolutionary stability of engineered genomes to improve their longevity.

• DOI: 10.1093/synbio/ysab018
• 发表时间: 2021
• 期刊: Synthetic biology (Oxford, England)
• 作者: Nuismer SL;C Layman N;Redwood AJ;Chan B;Bull JJ
• 通讯作者: Bull JJ