Evaluating causes of mumps reemergence with computational modeling

项目摘要/摘要 几千年来，传染病导致急性疾病、长期并发症和死亡。发明了 安全有效的疫苗使医疗保健发生了革命性的变化，使个人能够获得保护性免疫 对抗病原体，而不受疾病和并发症之苦。但是，最近，疫苗是可以预防的 疾病正在全国范围内重新出现。我的长期目标是确定允许继续 在人类之间传播疫苗可预防的疾病以提高和维持大规模的疗效 使用计算传染病建模的疫苗接种计划。这项建议的目的是 通过调查最近再次出现的腮腺炎，告知并维持大规模疫苗接种的有效性。 目前的研究表明，腮腺炎卷土重来的两个可能原因：疫苗利用不足和疫苗接种 不匹配。这项提案将使用腮腺炎传播和疫苗接种的年龄结构计算模型。 根据疾病、人口统计和RNA序列数据进行校准，以确定疫苗之间的关系 使用情况和流行性腮腺炎暴发(目标1)，并评估流行性腮腺炎疫苗随时间的有效性(目标2)。 这项拟议的研究将为改进流行性腮腺炎疫苗接种提供科学建议。 战略(增强剂和/或疫苗改装)。拟议的研究还将产生计算 工具包括腮腺炎传播的校准模型。最后，该项目将培训一名调查员 过渡到使用计算模型来研究影响人类的传染病。发展，发展 专业知识，候选人将建立影响人类的新发传染病的模型(培训目标1)， 在公共卫生背景下解释计算传染病模拟结果(培训目标2)， 加深病毒对人类健康、人体免疫反应和疫苗接种的重要知识(培训 目标3)，并培养所需的技能，以执行全国范围内对可预防的再生疫苗进行建模的研究 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、会议出席、研讨会、研究交流和指导研究。一位高度 由具有互补专业知识的合格导师和合作者组成的团队将指导研究和培训 议程。该培训计划将建立一个独立的研究计划，使用计算感染性 将在R01提案中使用的病毒生态/进化组合框架中的疾病建模 调查已确定的腮腺炎驱动因素的预期状态和地区差异。总而言之，这项研究将 科学地告知更有效的疫苗接种策略。这项建议涉及NIAID的几项研究 优先事项：(1)传染病病原体的建模；(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.