Integrating data streams with multi-scale modeling to guide norovirus vaccine decision-making

项目总结 诺如病毒每年在美国造成超过2000万例腹泻病例，占所有腹泻病例的五分之一 在全球范围内，全球有超过20万人死亡。诺沃克病毒疫苗目前正在开发中。我们的目标是 开发全面、详细、用户友好的诺沃克病毒传播和疫苗接种模拟器，将有助于 指导和通报诺如病毒疫苗的设计和实施。 为了实现这一目标，需要一些具体的见解和参数估计，例如：以什么速度 个体对诺沃克病毒的免疫力是否会减弱？先前的感染(或接种疫苗)如何影响流行性感冒的进程 疾病和病毒脱落的持续时间/数量？交叉保护豁免权的程度是多少 基因组、基因型别和菌株水平？有了这样的结果，我们可以回答以下疫苗策略 问题：控制需要重新接种疫苗的频率是多少？诺沃克病毒疫苗需要多久接种一次 更新以跟上病毒发展的步伐？以年龄为目标的(或 其他)疫苗接种策略？ 为了回答这些问题，我们将整合来自多个来源的详细数据，包括志愿者感染 研究、国家监测和病毒序列数据集。我们将使数学和统计模型适用于 这些数据集来回答上面提出的问题。我们的分析将提供对 病毒的流行病学和进化动态。这些信息将被用来开发和 实施详细的诺沃克病毒传播和疫苗接种模拟器。此模拟器将打包为 为疫苗设计者和政策执行者提供用户友好的应用程序，以分析和预测可能发生的情况 疫苗配方和分发策略的影响。

PROJECT SUMMARY Noroviruses cause over 20 million diarrhea cases annually in the United States, one-fifth of all diarrhea cases globally, and over 200,000 deaths worldwide. Norovirus vaccines are currently in development. Our goal is to develop a comprehensive detailed, user-friendly norovirus transmission and vaccination simulator that will help guide and inform norovirus vaccine design and implementation. To achieve this goal, a number of specific insights and parameter estimates are required, such as: At what rate does immunity to norovirus wane in individuals? How does prior infection (or vaccination) affect the course of illness and the duration/quantity of viral shedding? What is the degree of cross-protecting immunity at the genogroup, genotype and strain-level? With such results in hand, we can answer the following vaccine strategy questions: What frequency of re-vaccination is required for control? How often will a norovirus vaccine need to be updated to keep up with viral evolution? What are the population-level health impacts of age-targeted (or other) vaccination strategies? To answer these questions, we will integrate detailed data from multiple sources including volunteer infection studies, national surveillance, and viral sequence datasets. We will fit mathematical and statistical models to these datasets to answer the questions posed above. Our analyses will provide a thorough understanding of the epidemiological and evolutionary dynamics of the virus. This information will be used to develop and implement a detailed norovirus transmission and vaccination simulator. This simulator will be packaged as a user-friendly application for vaccine designers and policy implementers to analyze and forecast possible impacts of vaccine formulations and distribution strategies.