An experimental vaccine composed of a genetically modified bacterium closely related to the bacterium that causes tuberculosis (TB) has been found to protect mice against TB infection, according to a study appearing online September 4 in the journal Nature Medicine. The research was funded in part by the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health.
TB, a respiratory disease that according to World Health Organization estimates killed 1.7 million people worldwide in 2009, is caused by the bacterium Mycobacterium tuberculosis (Mtb). A vaccine to prevent TB infection, called bacille Calmette-Guérin (BCG), is widely available, but it confers limited protection and can cause severe TB infection in infants infected with HIV, restricting its use in certain countries.
In the new study, led by William R. Jacobs, Jr., Ph.D., of the Albert Einstein College of Medicine in New York, researchers genetically modified M. smegmatis, a relative of Mtb that is generally harmless to humans. Specifically, the scientists replaced a set of M. smegmatis genes called esx-3, believed to be important because its DNA sequence is unusually consistent across species, with the corresponding but not identical set of genes from Mtb. They vaccinated mice with this modified form of M. smegmatis, essentially delivering the Mtb version of esx-3 without the bacterial components that would cause infection, and then challenged the mice with Mtb. In mice that received the experimental vaccine, levels of TB bacteria were 1,000 times lower than in those that received BCG. This suggests that modified M. smegmatis induces a strong immune response in mice that can protect them from TB.
The study authors are encouraged by their study results, but they caution that further testing of the modified M. smegmatis TB vaccine is needed before it might be evaluated in human clinical trials.
KA Sweeney et al. A recombinant Mycobacterium smegmatis induces potent bactericidal immunity against M. tuberculosis. Nature Medicine DOI: 10.1038/nm2420 (2011).
Christine Sizemore, Ph.D., chief of NIAID's Tuberculosis and Other Mycobacterial Diseases Section, is available to discuss this study.
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