Globally, tuberculosis remains the number one killer in adults. Moreover, multi-drug-resistant tuberculosis strains are on the rise which cannot be treated by first-line drugs. A vaccine against tuberculosis, termed BCG is available which, however, fails to protect against the most frequent form of disease, pulmonary tuberculosis in adults. A more efficient vaccine is urgently needed for control of this global threat.
Recombinant BCG, which express listeriolysin and is deleted for the urease gene, has been created and shown to stimulate far more efficacious protection against tuberculosis than the BCG vaccine currently in use. This new vaccine induces cell death in infected host cells, which leads to stimulation of protection by dendritic cells, the most efficacious antigen-presenting cells. As a result, stronger protection against pulmonary tuberculosis has been achieved in preclinical studies. Importantly, the new vaccine also protects against clinical isolates of the Beijing family. These clinical isolates are frequently multi-drug-resistant and more aggressive and hence have started to conquer the globe. It has been assumed that the Beijing isolates emerged in response to drug treatment and vaccination. The new genetically engineered BCG could provide an efficacious measure against this threat.