Designing tuberculosis vaccine efficacy trials – lessons from recent studies

Ann M Ginsberg

doi:10.1080/14760584.2019.1593143

Abstract

ABSTRACTIntroduction: Tuberculosis (TB) is the leading infectious killer globally and new TB vaccines will be crucial to ending the epidemic. Since the introduction in 1921 of the only currently licensed TB vaccine, BCG, very few novel vaccine candidates or strategies have advanced into clinical efficacy trials.Areas covered: Recently, however, two TB vaccine efficacy trials with novel designs have reported positive results and are now driving new momentum in the field. They are the first Prevention of Infection trial, evaluating the H4:IC31 candidate or BCG revaccination in high-risk adolescents and a Prevention of Disease trial evaluating the M72/AS01E candidate in M.tuberculosis-infected, healthy adults. These trials are briefly reviewed, and lessons learned are proposed to help inform the design of future efficacy trials. The references cited were chosen by the author based on PubMed searches to provide context for the opinions expressed in this Perspective article.Expert opinion: The opportunities created by these two trials for gaining critically important knowledge are game-changing for TB vaccine development. Their results clearly establish feasibility in the relatively near term of developing novel, effective vaccines that could be crucial to ending the TB epidemic.

Highlights

Tuberculosis (TB) is the leading infectious killer globally and new TB vaccines will be crucial to ending the epidemic
In a unique occurrence for TB vaccine development, two clinical efficacy trials published their results in 2018: a prevention of Mycobacterium tuberculosis (Mtb) infection (POI) trial of Statens Serum Institut’s and its partner’s, Sanofi Pasteur’s, novel subunit candidate vaccine, H4:IC31®, or Bacille Calmette-Guérin (BCG) revaccination compared to placebo in Mtb-uninfected, HIV-uninfected, healthy adolescents at high risk of Mtb infection ([26]; NCT02075203), and a prevention of active TB disease trial of GlaxoSmithKline’s candidate, M72/AS01E, compared to placebo in healthy, Mtbinfected adults, which recently published its primary analysis ([27]; NCT01755598)
Once the final results of the second trial are published, full safety, immunogenicity, and efficacy data will be available for three vaccine candidates (H4:IC31, BCG revaccination and M72/AS01E) – an unprecedented treasure trove of human data for this field

Summary

Introduction

Tuberculosis (TB) is the leading infectious killer globally and new TB vaccines will be crucial to ending the epidemic. Areas covered: Recently, two TB vaccine efficacy trials with novel designs have reported positive results and are driving new momentum in the field They are the first Prevention of Infection trial, evaluating the H4:IC31 candidate or BCG revaccination in high-risk adolescents and a Prevention of Disease trial evaluating the M72/AS01E candidate in M.tuberculosis-infected, healthy adults. Expert opinion: The opportunities created by these two trials for gaining critically important knowledge are game-changing for TB vaccine development. Their results clearly establish feasibility in the relatively near term of developing novel, effective vaccines that could be crucial to ending the TB epidemic.

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Results

Conclusion