Background Tuberculosis (TB) remains a leading cause of infectious disease death. New TB vaccines are currently in late-stage trials and may be available before the end of the decade. Modelling predicts new TB vaccines may reduce global burden but rely on assumptions about vaccine efficacy by TB disease stage and TB natural history, which may be incorrect. We explored the sensitivity of estimates of the impact of new TB vaccines to uncertainties in efficacy by disease stage and natural history. Methods and findings We developed a dynamic compartmental TB model for India, including early TB disease stages (non-infectious disease, infectious asymptomatic disease, and infectious symptomatic disease). Scenarios assumed 50% vaccine efficacy for 10 years and prevented progression to (a) only infectious symptomatic disease, or (b) any infectious disease (infectious asymptomatic disease and infectious symptomatic disease), or (c) any disease (non-infectious disease, infectious asymptomatic disease, and infectious symptomatic disease). We estimated impact on averting disease episodes over 2030–2050, compared to no-new-vaccine introduction. Results suggest, over 3 years, there was little difference in the proportion of cumulative symptomatic disease episodes averted by vaccines preventing only infectious symptomatic disease, any infectious disease, or any disease (1.6%, 2.3%, and 2.3%, respectively). However, over 20 years, compared to vaccines preventing only infectious symptomatic disease, vaccines preventing any infectious disease, or any disease, averted a markedly higher proportion of symptomatic disease episodes (7.3%, 19.4%, and 23.3%, respectively), due to preventing continued transmission from infectious asymptomatic disease. A key limitation with any mathematical modelling study is the uncertainty associated with the inputs, and further data collection is required to better understand the transmissibility, morbidity, and dynamics of asymptomatic disease, to improve modelling estimates and inform wider policy. Conclusions Our modelling estimates that the population impact of new TB vaccines may depend on efficacy against infectious asymptomatic disease. TB vaccine trials should include analyses of participant sputum samples (collected during or at the end of trials and analysed at the end of trials) to enable better estimates of the potential value of new TB vaccines against infectious asymptomatic disease.
Tanvir et al. (2026) studied this question.