New tuberculosis vaccines: From research to application

A large European consortium has joined forces to deliver new vaccine candidates against tuberculosis (TB). The identification of promising vaccination antigens and disease-specific biomarkers could improve the dismal prognosis of TB in the near future.

TB constitutes one of the deadliest infectious diseases worldwide with millions of deaths every year. Although the causative agent Mycobacterium tuberculosis (MTB) can be treated with antibiotics to some extent, the emergence of drug-resistant bacterial strains hampers the effectiveness of the treatment.

As a result, the development of preventative TB vaccines is of paramount importance for controlling disease spread. The currently available Bacille Calmette–Guérin (BCG) vaccine is only efficacious against specific forms of childhood TB and confers no protection to adults.

Seeking to address this, the EU-funded 'Discovery and preclinical development of new generation tuberculosis vaccines' NEWTBVAC project was designed to test novel vaccines against MTB. The consortium based their strategy on the European TB vaccine pipeline to identify and forward promising vaccine candidates into the clinical trial stage.

Hitherto unknown Mycobacterium antigens were tested in animal models for their ability to raise protective immune responses against the bacteria. Alongside administration routes and doses, antigen-delivery systems were optimised in animal experiments to achieve the most efficacious combination. Partners also explored the development of new live vaccines based on the BCG strain that had impaired vital processes such as intracellular trafficking and nutrient uptake.

With respect to TB-related biomarkers, the objective was to discriminate patients with active disease from those with latent infection at the molecular level. To this end, researchers performed a transcriptomic analysis of blood from untreated, cured TB patients as well as latently infected individuals. They unravelled disease-associated gene expression patterns and identified biomarkers related to lung remodelling.

A phase I trial of the recombinant VPM1002 candidate vaccine was completed in an endemic area in South Africa. Evaluation of the MTBVAC vaccine candidate in an approved clinical trial in Switzerland will dictate its future use in a clinical setting.

Taken together, the activities of the NEWTBVAC consortium aimed to sustain the TB vaccine research pipeline and advance any promising candidates to clinical stages. Coupled with the developed disease-monitoring tools, the project deliverables are set to confer improved protection to infected individuals.

related link: http://cordis.europa.eu/result/brief/rcn/11352_en.html