Estimating the Epidemiologic Impact of TB Vaccines using Mathematical Models

项目摘要/摘要 结核病(TB)是导致健康状况不佳的主要原因，是2019年死亡的主要传染病原因，这是一种负担 在低收入和中等收入国家，这种感觉不成比例。加快实现世界卫生目标的进程 该组织雄心勃勃的目标是到2035年将结核病死亡人数减少95%，病例减少90%，这是预防结核病的新工具 是必不可少的。新的和重新调整用途的结核病疫苗有望填补这一空白：经过数十年的研究， 两种结核病疫苗已从第二阶段临床试验中出现，疗效呈阳性结果。现有的卡介苗 目前在出生时接种的疫苗，在进行了IIb期试验后，正在重新考虑用于成人(重新接种) 在预防青少年结核病感染方面显示出50%的效果。在另一项IIb期试验中，亚单位疫苗 M72-AS01E对成人结核病的预防效果为50%。的总体目标 这份K01是为了(1)评估新的和改变用途的结核病疫苗的潜在流行病学影响；以及(2) 确定和评估针对高危人群的潜在疫苗接种战略。我们将使用来自 GlobalMix研究，将提供来自四个国家的详细的特定国家的社交联系和流动性数据 莫桑比克、危地马拉、印度和巴基斯坦--结核病流行概况各不相同的国家。理解 各国疫苗影响的潜在差异可以指导进一步的疫苗试验和设计 告知将新的和重新调整用途的结核病疫苗引入免疫计划的战略。这个K01 该项目将为纳尔逊博士提供进行国际实地工作以及建造、装修和 分析结核病传播模型，以解决对结核病疫苗政策和 实施。指导团队：Ben Lopman博士(首席导师)，Neel Gandhi博士(共同导师)，Ted 科恩(联合导师)和罗布·布雷曼(联合导师)将为纳尔逊博士提供如何建立和 分析结核病传播模型，以评估疫苗的影响、疫苗试验的设计和实施，以及 建模在制定循证的国家和全球疫苗政策中的作用。埃默里的故乡 埃默里大学疫苗中心和结核病研究中心为年轻人提供丰富的资源 从事结核病疫苗研究的研究人员为开展拟议的工作提供了理想的环境。这个 在本K01中开发的结核病疫苗建模框架将形成未来NIH R01提案的基础，旨在 量化国家一级疫苗的影响并制定针对国家的结核病疫苗建议 与结核病疫苗专家和政策制定者共同实施。纳尔逊博士将发展的技能 对其他传染病有广泛的适用性，为传染病的职业生涯奠定了基础 将解决新出现和地方性感染的疫苗实施挑战。

PROJECT SUMMARY/ABSTRACT Tuberculosis (TB) is a major cause of ill health and was the leading infectious cause of death in 2019, a burden felt disproportionately in low- and middle-income countries. To accelerate progress towards the World Health Organization’s ambitious goal to cut TB deaths by 95% and cases by 90% by 2035, new tools to prevent TB are essential. New and repurposed vaccines against TB hold promise to fill this gap: after decades of research, two TB vaccines have emerged from Phase II clinical trials with positive efficacy results. The existing BCG vaccine, currently given at birth, is being reconsidered for use (‘revaccination’) in adults after a Phase IIb trial showed 50% efficacy in preventing TB infection in adolescents. In a separate Phase IIb trial, subunit vaccine M72-AS01e was shown to be 50% efficacious in preventing TB disease in adults. The overarching objectives of this K01 are to (1) estimate the potential epidemiologic impact of new and repurposed TB vaccines; and (2) identify and assess potential vaccination strategies targeting high-risk groups. We will do this using data from the GlobalMix study, which will provide detailed country-specific social contact and mobility data from four countries – Mozambique, Guatemala, India, and Pakistan – with diverse TB epidemic profiles. Understanding potential differences in vaccine impact across countries can guide the design of further vaccine trials and inform strategies for introducing new and repurposed TB vaccines into immunization programs. This K01 project will provide Dr. Nelson with skills in conducting international field work as well as building, fitting, and analyzing TB transmission models to address questions with practical implications for TB vaccine policy and implementation. The mentoring team, Drs. Ben Lopman (Primary Mentor), Neel Gandhi (co-Mentor), Ted Cohen (co-Mentor), and Rob Breiman (co-Mentor), will provide Dr. Nelson with training in how to build and analyze models of TB transmission to estimate vaccine impact, the design and conduct of vaccine trials, and the role of modeling in development of evidence-based national and global vaccine policy. Home to the Emory Vaccine Center and the Center for TB Research, Emory University offers abundant resources for young investigators engaged in TB vaccine research, providing an ideal setting to carry out the proposed work. The TB vaccine modeling framework developed in this K01 will form the basis of a future NIH R01 proposal aiming to quantify country-level vaccine impact and develop country-specific recommendations for TB vaccine implementation in conjunction with TB vaccine experts and policymakers. The skills Dr. Nelson will develop have broad applicability to other infectious diseases, building a foundation for a career in infectious disease dynamics which will address vaccine implementation challenges for emerging and endemic infections.