The Epidemiological and Economic Gains of Introducing the M72/AS01 <sub>E</sub> Vaccine in India and Indonesia – A Modeling Study

Abstract

Background: A recent phase 2b trial of the M72/AS01E candidate tuberculosis vaccine demonstrated 49.7%-54.1% protection against progression from latent to active pulmonary tuberculosis in populations previously unexposed to HIV. To determine if investment in a phase 3 trial is justifiable, epidemiological and economic impacts in India and Indonesia were estimated. Methods: Vaccine impact was modeled using a deterministic, age structured TB transmission dynamics model, for efficacies 49.7% and 54.1% and duration of protection lasting lifetime or 10 years. Economic impact was estimated from 2020 to 2050, in terms of full-income, based on annual mortality risk reductions, using the value-of-a-statistical-life year in each country. Impact on cause-eliminated life expectancy was additionally calculated. Results: In India, 53.8 million incident cases can give rise to 8.8 million TB deaths and US$6.6 trillion in economic losses; in Indonesia, to 23.3 million incident cases, 3.2 million TB deaths and US$2.9 trillion in economic losses. Vaccination, if initiated in 2025 to the 18-49 year old population, reduces 19% of TB deaths in India and 12% of TB deaths in Indonesia, contributing to 22.5% and 12.9% reductions in economic losses, respectively. Vaccinating populations of all ages, reduces 25.8% of TB deaths in India and 21.5% of TB deaths in Indonesia, with 30.3% and 23% reductions in economic losses, respectively. Delaying vaccination until 2030, to the 18-49 year old population, reduces 12.8% and 8% of TB deaths, with 16% and 8.8% reductions in economic losses. By extending vaccination to populations of all ages, 18.2% and 15.1% of TB deaths and 22.6% and 16.6% in economic losses, can be averted. In the best case, vaccination can prevent 27.5% and 20.7% of life expectancy losses at birth, respectively. Interpretation: If up to a third of economic losses and a quarter of TB deaths in India, and a quarter of TB deaths and economic losses in Indonesia can be averted, then investment in a phase 3 trial is a worthy consideration. Longer-term economic gains are potentially even larger, given the impact on life expectancy in peak productive ages. The window for realizing these gains is fast approaching. Funding Statement: SFA and LJA: NPRP grant number 7-627-3-167 from the Qatar National Research Fund (a member of 29 Qatar Foundation) Declaration of Interests: We declare that we have no conflicts of interest.