Estimating the Epidemiologic Impact of TB Vaccines using Mathematical Models

项目总结/摘要 结核病（TB）是健康状况不佳的主要原因，也是2019年死亡的主要传染病原因， 在低收入和中等收入国家，这种情况尤为严重。加快实现世界卫生组织 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%，预防结核病的新工具 是必不可少的。新的和重新利用的结核病疫苗有望填补这一空白：经过几十年的研究， 两种结核病疫苗已从第二阶段临床试验中获得了积极的疗效结果。现有BCG 目前在出生时接种的疫苗，在IIb期试验后正在重新考虑用于成人（“再接种”） 在预防青少年结核病感染方面显示出50%的有效性。在一项单独的IIb期试验中，亚单位疫苗 M72-AS 01 e在预防成人结核病方面的有效性为50%。的总体目标 本K 01的目的是（1）估计新的和再利用的结核疫苗的潜在流行病学影响;以及（2） 确定和评估针对高危群体的潜在疫苗接种战略。我们将使用以下数据来实现这一点： 全球混合研究将提供来自四个国家的详细的具体国家社会联系和流动数据， 这些国家包括莫桑比克、危地马拉、印度和巴基斯坦，结核病流行情况各异。理解 各国疫苗影响的潜在差异可以指导进一步疫苗试验的设计， 为在免疫规划中引入新的和重新利用的结核病疫苗提供信息。K01 该项目将为纳尔逊博士提供进行国际实地工作以及建筑，装修和 分析结核病传播模型，以解决对结核病疫苗政策具有实际意义的问题， 实施.指导团队，本·洛普曼博士（初级指导员），尼尔·甘地博士（共同指导员），特德· 科恩（共同导师）和罗布Breiman（共同导师），将提供纳尔逊博士的培训，如何建立和 分析结核病传播模型，以估计疫苗的影响、疫苗试验的设计和实施，以及 建模在制定基于证据的国家和全球疫苗政策中的作用。埃默里之家 埃默里大学疫苗中心和结核病研究中心为年轻人提供了丰富的资源 研究人员从事结核病疫苗研究，提供了一个理想的环境，开展拟议的工作。的 本K 01中开发的结核病疫苗建模框架将成为未来NIH R 01提案的基础， 量化国家一级疫苗的影响，并制定针对具体国家的结核病疫苗建议 与结核病疫苗专家和决策者共同实施。纳尔逊博士将发展的技能 对其他传染病有广泛的适用性，为从事传染病职业奠定了基础 这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.