Study leader William R. Jacobs Jr. of the Albert Einstein College of Medicine in New York says TB, a disease that kills an estimated 1.7 million worldwide, is caused by the bacterium Mycobacterium tuberculosis.
A vaccine to prevent TB infection, called bacille Calmette-Guerin, is widely available, but it provides limited protection and can cause severe TB infection in infants infected with HIV, restricting its use in certain countries, Jacobs says.
Jacobs and colleagues genetically modified M. smegmatis, a relative of Mycobacterium TB that is generally harmless to humans, by replacing 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 Mycobacterium TB.
The researchers vaccinated mice with the modified form of M. smegmatis, essentially delivering the Mycobacterium TB version of esx-3 without the bacterial components that would cause infection and then challenged the mice with Mycobacterium TB.
The study, published in the journal Nature Medicine, finds in mice that received the experimental vaccine, levels of TB bacteria were 1,000 times lower than in those that received bacille Calmette-Guerin, suggesting that modified M. smegmatis induces a strong immune response in mice that can protect them from TB.