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

项目摘要 在美国，诺如病毒每年导致超过2000万例腹泻病例，占所有腹泻病例的五分之一 全球范围内，超过200，000人死亡。诺如病毒疫苗目前正在开发中。我们的目标是 开发一个全面详细、用户友好的诺如病毒传播和疫苗接种模拟器， 指导并告知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： 个体对诺如病毒的免疫力是否减弱？既往感染（或疫苗接种）如何影响 疾病和病毒脱落的持续时间/数量？交叉保护免疫力的程度是什么 基因组、基因型和菌株水平？有了这样的结果在手，我们可以回答以下疫苗策略 问题：需要多长时间进行一次复种？诺如病毒疫苗需要多久接种一次 更新以跟上病毒的进化吗针对年龄的（或 疫苗接种策略？ 为了回答这些问题，我们将整合包括志愿者感染在内的多个来源的详细数据 研究、国家监测和病毒序列数据集。我们将拟合数学和统计模型， 这些数据集来回答上述问题。我们的分析将提供一个透彻的理解， 病毒的流行病学和进化动力学。这些信息将用于开发和 实施详细的诺如病毒传播和疫苗接种模拟程序。该模拟器将打包为 方便疫苗设计者和政策执行者分析和预测可能的 疫苗配方和分配战略的影响。

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.