Successes and failures in human tuberculosis vaccine development

ABSTRACT

Introduction: Tuberculosis (TB) is an infectious disease caused mainly by Mycobacterium tuberculosis. In 2016, the WHO estimated 10.5 million new cases and 1.8 million deaths, making this disease the leading cause of death by an infectious agent. The current and projected TB situation necessitates the development of new vaccines with improved attributes compared to the traditional BCG method.

Areas covered: In this review, the authors describe the most promising candidate vaccines against TB and discuss additional key elements in vaccine development, such as animal models, new adjuvants and immunization routes and new strategies for the identification of candidate vaccines.

Expert opinion: At present, around 13 candidate vaccines for TB are in the clinical phase of evaluation; however, there is still no substitute for the BCG vaccine. One major impediment to developing an effective vaccine is our lack of understanding of several of the mechanisms associated with infection and the immune response against TB. However, the recent implementation of an entirely new set of technological advances will facilitate the proposal of new candidates. Finally, development of a new vaccine will require a major coordination of effort in order to achieve its effective administration to the people most in need of it.

KEYWORDS:

• Tuberculosis
• vaccine
• development
• BCG
• challenges

Article highlights

• This review describes the current state of development of vaccines against Tb, considering vaccines in both the experimental and clinical trial stage.

• A description of the animal models used for tuberculosis vaccine research is included and the urgent requirement for inclusion of the concepts of replacement, reduction and refinement of animal use in testing is highlighted.

• The impact of new procedures such as reverse vaccinology, proteomics and plant-based expression of Tb antigens is discussed, as well as their potential contribution in the development of new Tb vaccines.

• The development and use of new adjuvants and delivery systems are described and the future of mucosal immunization and the new concept of trained immunity in Tb is discussed.

• Finally, the biological, social and economic difficulties faced by new future tuberculosis vaccines are discussed, highlighting the need for a new paradigm to meet this challenge.

This box summarizes key points contained in the article.

Declaration of Interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This manuscript was funded by CONACyT Proyecto de Desarrollo Científico para Atender Problemas Nacionales 213712.