Clinical trials of tuberculosis vaccines in the era of increased access to preventive antibiotic treatment.

Approximately 10·6 million people worldwide develop tuberculosis each year, representing a failure in epidemic control that is accentuated by the absence of effective vaccines to prevent infection or disease in adolescents and adults. Without effective vaccines, tuberculosis prevention has relied on testing for Mycobacterium tuberculosis infection and treating with antibiotics to prevent progression to tuberculosis disease, known as tuberculosis preventive treatment (TPT). Novel tuberculosis vaccines are in development and phase 3 efficacy trials are imminent. The development of effective, shorter, and safer TPT regimens has broadened the groups eligible for TPT beyond people with HIV and child contacts of people with tuberculosis; future vaccine trials will be undertaken in an era of increased TPT access. Changes in the prevention standard will have implications for tuberculosis vaccine trials of disease prevention, for which safety and sufficient accrual of cases are crucial. In this paper, we examine the urgent need for trials that allow the evaluation of new vaccines and fulfil the ethical duty of researchers to provide TPT. We observe how HIV vaccine trials have incorporated preventive treatment in the form of pre-exposure prophylaxis, propose trial designs that integrate TPT, and summarise considerations for each design in terms of trial validity, efficiency, participant safety, and ethics.

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Déclaration de conflit d'intérêts

Declaration of interests GC reports research funding from the US National Institutes of Health (NIH)/Division of AIDS (UM1AI068614, UM1AI068636, 5UM1AI154463). Since March, 2022, MQ has worked full time as an employee of Evidera, a commercial research organisation that receives funding to conduct research on behalf of private pharmaceutical companies; this research is unrelated to the topic of this Personal View. RGW acknowledges project funding from the Wellcome Trust (218261/Z/19/Z), NIH (1R01AI147321-01), European and Developing Countries Clinical Trials Partnership (RIA208D-2505B), UK Medical Research Council (CCF17-7779 via SET Bloomsbury), UK Economic and Social Research Council (ES/P008011/1), Bill & Melinda Gates Foundation (OPP1084276, OPP1135288 & INV-001754), and WHO (2020/985800-0). All other authors declare no competing interests.