Estimating the Epidemiologic Impact of TB Vaccines using Mathematical Models

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.

结核病（Tuberculosis, TB）是引发健康损害的主要病因，2019年更是头号致死性传染病，其疾病负担在中低收入国家尤为凸显。为加速实现世界卫生组织（World Health Organization）到2035年将结核病死亡数降低95%、病例数降低90%的宏伟目标，亟需全新的结核病防控工具。新型及再利用型结核病疫苗有望填补这一空白：历经数十年研究，已有两款结核病疫苗通过II期临床试验并展现出积极的保护效力。当前临床使用的卡介苗（BCG vaccine）通常在新生儿出生时接种，此前一项IIb期临床试验显示其可使青少年结核病感染预防有效率达50%，因此学界正重新考量其在成人群体中的复种方案。另一项独立IIb期临床试验则证实，亚单位疫苗M72-AS01e可使成人结核病发病预防有效率达50%。本K01项目的总体目标为：（1）评估新型及再利用型结核病疫苗的潜在流行病学影响；（2）甄别并评估针对高危人群的潜在疫苗接种策略。本研究将依托GlobalMix研究（GlobalMix study）展开，该研究将从莫桑比克、危地马拉、印度及巴基斯坦这四个结核病流行特征各异的国家，收集详尽的国家层面社会接触与人口流动数据。明晰不同国家间疫苗影响的潜在差异，可为后续疫苗临床试验的设计提供指导，并为将新型及再利用型结核病疫苗纳入免疫规划的策略制定提供依据。