Scientists stumbled upon a new tuberculosis vaccine with much higher immune response than BCG.
A possible new vaccine has been found to eliminate tuberculosis bacteria from infected tissues in some mice. The research, reported in the September 4 edition of Nature Medicine, describes the immunization potential of an altered strain of the related bacteria Myobacterium smegmatis.
Tuberculosis, which is caused by Myobacterium tuberculosis, is responsible for two to three million deaths per year. The only tuberculosis vaccine in current use, called Bacille Calmette-Guérin (BCG), has been inconsistently effective at protecting against the disease.
Scientists involved in the research first tested the function of a set of myobacteria genes called esx-3, which are responsible for protecting the bacteria against hosts’ first-line immune defense. Since removing these genes from M. tuberculosis would render the bacteria unable to survive, the scientists removed them instead from the closely related bacteria M. smegmatis.
Mice injected with doses of the altered bacteria that would usually be sufficient to kill them were unaffected, presumably because the immune system was able to locate and eliminate them. The scientists termed the modified strain of M. smegmatis “IKE” for immune killing evasion.
Next, the scientists inserted esx-3 genes from M. tuberculosis into M. smegmatis and injected the altered bacteria (termed IKEPLUS) into the same mice. Their assumption was that this would restore the bacteria’s ability to evade the mouse immune system, but in fact it inspired an unusually strong immune response.
The scientists hypothesized that they had stumbled on a novel way of immunizing mice against tuberculosis. To test their hypothesis, they exposed five IKEPLUS-immunized mice and five control mice to massive doses of tuberculosis bacteria. The five control mice were all dead within days, while all the IKEPLUS-immunized mice survived at least 40 days after infection, two survived 90 days, and one 343 days.
In later experiments, the scientists found that IKEPLUS immunization offered better protection to mice than the established BCG vaccine. In addition, IKEPLUS-immunized mice that survived more than 200 days after exposure to M. tuberculosis were found to have none of the bacteria in their livers. Nonetheless, there remains room for improvement as only 20 percent of mice survived for long periods after IKEPLUS immunization.