Estimating the Epidemiologic Impact of TB Vaccines using Mathematical Models

使用数学模型估计结核疫苗的流行病学影响

• 批准号: 10686111
• 负责人: Kristin Nicole Bratton Nelson
• 金额: $ 13.11万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-18 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10686111
• 关键词: Acceleration; Accounting; Address; Adolescent; Adult; BCG Vaccine; Behavior; Biological; Birth; Cause of Death; Cessation of life; Communicable Diseases; Country; Data; Development; Disease; Disease Surveillance; Disease model; Epidemic; Epidemiology; Foundations; Future; Goals; Guatemala; HIV/TB; Health; Herd Immunity; Home; Household; Human; Human Resources; Immunization Programs; Incidence; India; Infection; Infection prevention; International; Interview; Location; Mentors; Modeling; Morbidity - disease rate; Mozambique; Pakistan; Participant; Pattern; Persons; Phase; Phase II Clinical Trials; Policies; Policy Maker; Population; Prevalence; Recommendation; Reporting; Research; Research Personnel; Resources; Risk; Schools; Social Mobility; Source; Structure; Subunit Vaccines; Surveys; Testing; Time; Training; Tuberculosis; Tuberculosis Vaccines; United States National Institutes of Health; Universities; Vaccination; Vaccine Research; Vaccinee; Vaccines; Variant; Work; Workplace; World Health Organization; career; co-infection; community transmission; design; disease transmission; disorder prevention; epidemiologic data; evidence base; high risk; high risk population; implementation barriers; low and middle-income countries; mathematical model; mortality; novel vaccines; particle; prevent; programs; role model; skills; social contact; surveillance data; tool; transmission process; unvaccinated; vaccination schedule; vaccination strategy; vaccine distribution; vaccine trial

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.

项目概要/摘要 结核病 (TB) 是造成健康不良的主要原因，也是 2019 年主要的传染病死亡原因，是一种负担 低收入和中等收入国家的感受尤为严重。加速世界卫生事业的进展 该组织的雄心勃勃的目标是到 2035 年将结核病死亡人数减少 95%，病例数减少 90%，并推出预防结核病的新工具 是必不可少的。新的和改造后的结核病疫苗有望填补这一空白：经过数十年的研究， 两种结核病疫苗已通过二期临床试验，并取得了积极的疗效结果。现有卡介苗 目前在出生时接种的疫苗在 IIb 期试验后正在重新考虑在成人中使用（“再接种”） 在预防青少年结核病感染方面显示出 50% 的功效。在一项单独的 IIb 期试验中，亚单位疫苗 M72-AS01e 在预防成人结核病方面显示出 50% 的有效性。总体目标 该 K01 旨在 (1) 估计新的和改造后的结核病疫苗的潜在流行病学影响；和（2） 确定并评估针对高危人群的潜在疫苗接种策略。我们将使用来自的数据来做到这一点 GlobalMix 研究将提供来自四个国家的详细的特定国家的社会联系和流动性数据 莫桑比克、危地马拉、印度和巴基斯坦等结核病流行情况各异的国家。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 为将新的和重新利用的结核病疫苗引入免疫计划提供策略。这个K01 项目将为纳尔逊博士提供进行国际实地工作以及建筑、安装和安装的技能 分析结核病传播模型，以解决对结核病疫苗政策具有实际影响的问题 执行。指导团队，博士。 Ben Lopman（主要导师）、Neel Gandhi（共同导师）、Ted Cohen（联合导师）和 Rob Breiman（联合导师）将为 Nelson 博士提供有关如何构建和 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。埃默里大学所在地 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，为开展拟议工作提供了理想的环境。这 K01 中开发的结核病疫苗建模框架将构成未来 NIH R01 提案的基础，该提案旨在 量化国家级疫苗影响并制定针对具体国家的结核病疫苗建议 与结核疫苗专家和政策制定者共同实施。尼尔森博士将培养的技能 对其他传染病具有广泛的适用性，为传染病职业奠定基础 这将解决新出现和地方性感染的疫苗实施挑战。