Currently the only licensed TB vaccine is Bacille Calmette-Guérin (BCG). First introduced in 1921 and now the most widely given vaccine in the world, BCG protects infants and children from tuberculosis meningitis and severe forms of disseminated TB, but offers limited protection against pulmonary TB to adolescents and adults. A new vaccine that acts against pulmonary TB would offer a powerful, and possibly essential, tool for reaching zero tuberculosis deaths, new infections, and suffering and stigma. However, the road to a safe, efficacious TB vaccine is a long one, beset by many challenges, including our limited understanding of TB immunology, most notably the absence of biomarkers that correlate with protective immunity. The following recommendations outline priority areas for research and discovery.
- Prioritize the science behind biomarker discovery. Biomarkers of protective immunity (distinct biological characteristics that are indicative of an immune response) against TB are urgently needed to reduce the cost, time, and uncertainty of advancing candidates through the pipeline. Several research areas may offer complementary insights into biomarker discovery, including studies to identify correlates of risk of TB disease; efforts to create a human challenge model for TB, which would allow investigators to get an early look at whether vaccine candidates induce an immune response before launching larger clinical trials; and diverse efforts to explore human/MTB interaction.
- Optimize preclinical research by improving animal models. No animal models have been validated with human disease, and few models have tested candidate vaccines against the range of MTB strains observed in the field.
- Pursue innovation within clinical trials. Clinical-trials and basic-science researchers should work together to synergize research and discovery efforts. All clinical trials should collect serum and cell samples that can be retrospectively analyzed to search for biosignatures that might serve as correlates of risk. Researchers should also map innovative pathways within the current clinical development strategies, including head-to-head trials of vaccine candidates in early immunogenicity studies, and trials that combine different candidates representing novel antigen targets. The role of BCG in the prime-boost strategy should also be examined.
Activities in each of the above areas will require more funding, with a focus on enabling basic and translational science. In 2013, donors spent just US$95.2 million on TB vaccine R&D, well short of the US$380 million annual investment called for in the Stop TB Partnership’s 2011-2015 Global Plan to Stop TB. There are currently 16 TB vaccine candidates under active clinical development. The Treatment Action Group publishes the latest information on vaccine development in its annual Pipeline Report.