MIT biological engineers have identified several promising vaccine targets that could finally provide better protection against tuberculosis, the world’s deadliest infectious disease that kills more than 1 million people every year. The only current vaccine for TB, called BCG, was developed over 100 years ago from a weakened cow bacterium and poorly protects adults against pulmonary tuberculosis. Researchers faced a daunting challenge in screening more than 4,000 proteins produced by the Mycobacterium tuberculosis bacteria to find which ones might trigger a strong immune response.
The team infected human cells with the bacteria, then used mass spectrometry to identify which bacterial peptides appeared most often on cell surfaces where they could activate T cells. Out of thousands of proteins, they narrowed the field to 27 TB peptides from 13 proteins, and further testing showed that 24 of these successfully triggered T cell responses in people previously infected with TB. The researchers created experimental mRNA vaccines using proteins from the type 7 secretion system, finding that vaccines targeting cell lysosomes were 1,000 times more effective at inducing immune response than others. While the team currently has a mix of eight proteins they believe could protect most people against TB, they continue testing combinations with blood samples from around the world, with human trials likely still several years away but offering genuine hope for conquering this ancient killer.
