Evaluating causes of mumps reemergence with computational modeling

项目概要/摘要 几千年来，传染病导致急性疾病、长期并发症和死亡。的发明 安全有效的疫苗彻底改变了卫生保健，使个人能够获得保护性免疫力， 抵抗病原体而不受疾病和并发症的困扰。但最近，疫苗可以预防的 疾病在全国范围内重新出现。我的长期目标是确定允许持续 预防疫苗可预防的疾病在人间的传播，以提高和维持大规模 疫苗接种计划使用计算传染病建模。这项建议的目的是 通过调查最近流行性腮腺炎的重新出现，为大规模疫苗接种提供信息并保持其效力。 目前的研究表明，腮腺炎重新出现的两个可能原因：疫苗利用不足和疫苗 不匹配.这项建议将使用年龄结构的腮腺炎传播和疫苗接种的计算模型 用疾病、人口统计学和RNA序列数据进行校准，以确定疫苗与 利用和流行性腮腺炎爆发（目标1），并评价流行性腮腺炎疫苗的长期有效性（目标2）。 这项拟议的研究将提供基于科学的建议，以改善腮腺炎疫苗接种 策略（加强剂和/或疫苗重新配制）。这项研究还将产生计算 包括腮腺炎传播校准模型在内的工具。最后，该项目将培训一名调查员， 过渡到使用计算模型研究影响人类的传染病。发展 专业知识，候选人将模拟影响人类的重新出现的传染病（培训目标1）， 在公共卫生背景下解释计算传染病建模结果（培训目标2）， 加深对人类健康、人类免疫反应和疫苗接种重要的病毒知识（培训 目标3），并培养执行一项全国性研究所需的技能， 传染病（培训目标4）。培训目标将通过课程作业，指导阅读，指导 数据教程、出席会议、研讨会和研究交流以及指导研究。一个高度 由具有互补专长的合格导师和合作者组成的团队将指导研究和培训 议程这个培训计划将建立一个独立的研究计划， 将在R 01提案中使用的病毒生态学/进化综合框架中的疾病建模 调查确定的腮腺炎驱动因素的预期州和地区差异。这项研究将 为更有效的疫苗接种策略提供科学信息。该提案涉及NIAID的几项研究 优先事项：（1）传染病病原体建模，（2）疫苗接种后维持免疫力，（3） 了解人类免疫系统，（4）了解免疫系统的早期发育，以及 (5)了解老年人的免疫力。

PROJECT SUMMARY/ABSTRACT For millennia, infectious diseases caused acute illness, long-term complications, and death. The invention of safe and effective vaccines revolutionized health care, allowing individuals to mount protective immunity against pathogens without suffering from illness and complications. But, recently, vaccine-preventable diseases are reemerging nationwide. My long-term goal is to identify processes that allow continued transmission of vaccine-preventable diseases among humans to improve and maintain efficacy of large-scale vaccination programs using computational infectious disease modeling. The objective of this proposal is to inform and maintain the efficacy of large-scale vaccination by investigating recent mumps reemergence. Current research suggests two possible causes for mumps reemergence: vaccine underutilization and vaccine mismatch. This proposal will use age-structured computational models of mumps transmission and vaccination calibrated with disease, demographic, and RNA sequence data to determine the relationship between vaccine utilization and mumps outbreaks (aim 1) and evaluate effectiveness of the mumps vaccine over time (aim 2). The proposed research will provide science-based recommendations to improve the mumps vaccination strategy (boosters and/or vaccine reformulations). The proposed research will also generate computational tools including calibrated models of mumps transmission. Finally, this project will train an investigator to transition to use computational models for research on infectious diseases that affect humans. To develop expertise, the candidate will model a reemerging infectious disease that affects humans (training aim 1), interpret computational infectious disease modeling results in their public health context (training aim 2), deepen knowledge of virus important for human health, human immune responses, and vaccination (training aim 3), and develop skills needed to execute a nationwide study modeling reemerging vaccine-preventable infectious diseases (training aim 4). Training aims will be met through coursework, guided readings, guided data tutorials, conference attendance, seminars, and research exchanges, and guided research. A highly qualified team of mentors and collaborators with complementary expertise will guide research and training agendas. This training plan will establish an independent research program using computational infectious disease modeling in a combined viral ecology/evolutionary framework that will be used in an R01 proposal investigating anticipated state and regional differences in identified mumps drivers. Together, this research will scientifically inform more effective vaccination strategies. This proposal addresses several of NIAID’s research priorities: (1) modeling of infectious disease agents, (2) maintaining immunity after vaccination, (3) understanding the human immune system, (4) understanding early development of the immune system, and (5) understanding immunity in the elderly.