Recent developments in tuberculosis vaccines

Abstract

Substantial efforts have been made over the past decade to develop vaccines against tuberculosis. We review recent developments in tuberculosis vaccines in the global portfolio, including those designed for use in a prophylactic setting, either alone or as boosts to Bacille Calmette–Guérin, and therapeutic vaccines designed to improve chemotherapy. While there is no doubt that progress is still being made, there are limitations to our animal model screening processes, which are further amplified by the lack of understanding of the immunological responses involved and the precise type of long-lived immunity that new vaccines need to induce. The challenge ahead is to optimize the planning for advanced clinical trials in poor endemic settings, which could be greatly facilitated by identifying correlates of protection.

Keywords::

• animal models
• BCG-replacement strategies
• clinical development
• mucosal delivery route
• regulatory aspects
• tuberculosis vaccines

Financial & competing interests disclosure

This work was supported by grant BIO2011-23555 from Spanish Ministry of Economy and Competitiveness and European Commission FP7-funded NEWTBVAC 241745 and European & Developing Countries Clinical Trials Partnership (EDCP, http://www.edctp.org/)-funded Collaboration and Integration of Tuberculosis Vaccine Trials in Europe and Africa (EDCTP-TBTEA). J Gonzalo-Asensio and C Martin are co-inventors on a composition of matter patent ‘tuberculosis vaccine’ filed by the University of Zaragoza. The authors have no other 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 apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Although the current animal models are essential for moving vaccine candidates to clinical trials, there is a growing awareness of their limitations for screening processes. New animal models for latency, transmission and neonatal safety and protection are necessary.

• • It would be important to develop new vaccine candidates aimed at blocking infection and not just preventing disease.

• • Biomarkers (immunological correlates of protection and risk of disease) are needed to predict vaccine efficacy to help progress between clinical trials and shorten duration of costly efficacy evaluation. Gene expression profiling in early clinical and in subsequent efficacy trials could help identify potential biomarkers for specific vaccine-induced protection.

• • There appears to be a natural susceptibility to human tuberculosis, which Bacille Calmette–Guérin is not able to overcome. A more effective intradermal vaccine at birth, capable of inducing adequate immune memory holds potential to effectively respond to heterologous subunit regimens.

• • Switching to the natural route of infection for vaccine delivery of heterologous boosts may be a key for success.

• • Design of clinical trials should take into account impact of socio-economic conditions and co-infection with other pathogens/parasites, which could alter vaccine-induced immune responses and efficacy.