Summary

     To eliminate tuberculosis globally, a new, effective, and affordable vaccine is urgently needed, particularly for use in adults and adolescents in low-income and middle-income countries. We have created a roadmap that lists the actions needed to accelerate tuberculosis vaccine research and development using a participatory process. The vaccine pipeline needs more diverse immunological approaches, antigens, and platforms. Clinical development can be accelerated by validated preclinical models, agreed laboratory correlates of protection, efficient trial designs, and validated endpoints. Determining the public health impact of new tuberculosis vaccines requires understanding of a country’s demand for a new tuberculosis vaccine, how to integrate vaccine implementation with ongoing tuberculosis prevention efforts, cost, and national and global demand to stimulate vaccine production. Investments in tuberculosis vaccine research and development need to be increased, with more diversity of funding sources and coordination between these funders. Open science is important to enhance the efficiency of tuberculosis vaccine research and development including early and freely available publication of study findings and effective mechanisms for sharing datasets and specimens. There is a need for increased engagement of industry vaccine developers, for increased political commitment for new tuberculosis vaccines, and to address stigma and vaccine hesitancy. The unprecedented speed by which COVID-19 vaccines have been developed and introduced provides important insight for tuberculosis vaccine research and development.

Introduction

     With an estimated 10 million new cases and 1·۵ million deaths per year, tuberculosis is one of the most devastating infectious diseases worldwide.1 The global elimination of tuberculosis requires innovative interventions, including safe and more effective vaccines.2 The current vaccine, Bacille Calmette-Guérin (BCG), has low and inconsistent protective efficacy against pulmonary tuberculosis in adolescents and adults, who are the main source of transmission.3 WHO has set three goals for the development of new tuberculosis vaccines: a safe, effective, and affordable tuberculosis vaccine for adolescents and adults; an affordable tuberculosis vaccine for neonates and infants with improved safety and efficacy compared with BCG; and a therapeutic vaccine to improve tuberculosis treatment outcomes.4,  ۵,  ۶ A vaccine for adolescents and adults has the greatest potential to produce a rapid global health impact.7,  ۸

     The research and development of new tuberculosis vaccines has been slow, faced with scientific setbacks and poor funding.9,  ۱۰ Two phase 2b trials have shown protection signals against Mycobacterium tuberculosis infection for BCG revaccination and protection against tuberculosis disease for candidate M72/AS01E.11,  ۱۲,  ۱۳ With several tuberculosis vaccine candidates in the pipeline,14 there is an urgent need to prioritise resources to research and development efforts and for a common vision of the knowledge and evidence required to guarantee the impact of new tuberculosis vaccines at the population and patient levels.

Conclusion

     This research and development roadmap sets research priorities for the discovery, preclinical development, clinical development, preparation for introduction, and implementation of new tuberculosis vaccines. It brings together the views and visions of a broad range of stakeholders in the field that included researchers, end users, funders, regulators, and industry professionals. The overall call is for acceleration towards achieving health impact through new approaches in vaccine discovery, better validated animal models, more efficient clinical development, proactive mapping of postlicensure use and demand, and removing barriers to effective scale up. Tuberculosis vaccine research and development requires more funding and a more effective use of existing resources, open exchange of data, specimens, and results, and strong engagement with stakeholders at the political, commercial, public health, and community levels. The rapid development and deployment of COVID-19 vaccines provides several examples to build on. The next step is for the various actors to follow the roadmap.