TB Vaccine Research

TB is one of the most prevalent infections in the world, particularly in developing countries. Currently, the only available vaccine against TB is Bacille Calmette-Guérin (BCG), which has been administered to over three billion people, making it the most widely used vaccine in the world.

BCG was developed in the early 1920's and is based on a live but attenuated strain of Mycobacterium bovis, which is the species that causes TB in cattle and can also infect humans.

Although BCG is effective in protecting young children from TB disease, its efficacy among adolescents and young adults has shown considerable variation ranging from 0% to 80% protection, especially in TB endemic areas. It is also not recommended to give to individuals who are immunocompromised such as those who are infected with HIV. Therefore, the development of a new vaccine is essential if TB is to be controlled and ultimately eradicated.

The past two decades have seen a significant increase in the development of potential new vaccines for TB. This is due to advances in the discovery and characterisation of M. tuberculosis virulence factors, aided by the recent completion and publication of the species genome.

The development of a vaccine from a pool of potential candidates through clinical trials to delivery in a healthcare system is a costly and time-consuming process with a very high failure rate along the way. A number of groups from around the world are collaborating in major partnerships on vaccine development. Two main vaccine strategies are being pursued:

(1) A pre-infection vaccine delivered early in life improved from the current BCG vaccine.

(2) A post-exposure vaccine that would invoke immunity to clinical disease after infection.

The Stop TB Partnership Working Group on TB Vaccine Development has as its main aim to have at least one new vaccine licensed, launched and distributed for use by 2015. The European Union has invested ?32m in funding two large consortia (TB-VAC & MUVAPRED) to deliver new TB vaccines to early clinical trials to assess safety by 2008-09.

These consortia comprise members of academia and industry from 15 European and African countries with the aim of ensuring that scientific successes are translated into concrete health-care results.

Researchers in the TB-VAC project will select vaccines for TB that work in adults and are suitable for use in resource-poor settings and are safe for HIV-infected individuals. MUVAPRED (Mucosal Vaccines against Poverty Related Diseases) is aimed at stimulating local immunity to neutralise M. tuberculosis where the organism enters the body in the lungs. The focus is on developing vaccines that can be administered orally or as a nasal spray thus avoiding the risks involved in using needles.

Similar TB vaccine development programmes are being funded by the National Institutes of Health in America. The HPA Centre for Emergency Preparedness and Response is performing many of the essential pre-clinical evaluations in these international consortia to determine which vaccines will be selected for clinical trial.

Four vaccines under development in Europe and America have already successfully passed through pre-clinical evaluations and are now in Phase 1 clinical trials. These are two sub-unit vaccines based on fusion proteins, a recombinant BCG expressing an M. tuberculosis protein and an attenuated vaccinia virus (MVA) also expressing a TB antigen. The latter has already undergone Phase I and II trials in Oxford, and further trials are continuing in The Gambia. Another vaccine (a recombinant BCG expressing listeriolysin) is planned to enter Phase I clinical trials shortly.

The momentum to develop a new and more effective vaccine is gathering pace. Whilst there is still much work to be done, there is genuine optimism that a new effective vaccine can be delivered in the next ten years.

For more information please visit:

Centre for Emergency and Response or the HPA TB section