Scientists report new method for finding a tuberculosis vaccine

No vaccine reliably prevents tuberculosis, but new research has demonstrated a strategy for developing a vaccine that could effectively stop this leading cause of infectious disease mortality.

A multi-institutional team used a novel approach for identifying all possible vaccine targets against the disease-causing Mycobacterium tuberculosis (Mtb). They used mass spectroscopy to screen all 4,000 proteins in the bacterium for potential vaccine targets (antigens), looking for those that are presented to the immune system and can trigger an immune response.

The analyzed samples, which came from six human donors, revealed antigens previously tested in TB vaccine studies, but also showed new vaccine targets that that might be effective.

To see if these new vaccine targets would elicit an immune response, the researchers tested four of them in peripheral blood cells from several individuals with prior Mtb exposure and found them to be effective in triggering the immune system.

Testing vaccine candidates usually requires studies in transgenic mice or human clinical trials, but the research group demonstrated a method of using mass spectroscopy to rapidly generate in vitro, quantitative assays to test and optimize candidate TB vaccines, reporting their results in a recent issue of Science Translational Medicine.

Their research demonstrates a method for further identifying and characterizing antigens of interest and evaluating vaccine platforms, such as mRNA systems, to deliver those antigens for protection against disease.

Tuberculosis currently claims more lives worldwide than any other pathogen (other than COVID-19 did during the global pandemic), totaling 1.3 million in 2022, according to the World Health Organization.  The BCG vaccine protects children against TB that has spread to other organs but offers limited protection to adults. So, more effective vaccines are needed to protect teens and adults from potentially fatal pulmonary disease.

“Our results will inform the development of new TB vaccine candidates,” the scientists said. The research was led by Bryan Bryson and Owen Leddy of the Massachusetts Institute of Technology with collaborators including Mary Carrington of the Frederick National Laboratory for Cancer Research.