Tuberculosis (TB) infections kill an estimated 2 million people each year, even though TB drugs have been widely available for decades. Now a group in the Republic of Korea reports what they believe could be a potent new method of fighting TB: a combination of cheap drugs and a DNA vaccine.
The bacterium that causes TB (Mycobacterium tuberculosis) spreads through the air and slowly destroys the lungs and other tissues. But the bug's tenacity is what makes tuberculosis so deadly. Drugs work for while, but patients may get sick again because dormant bacteria within them "re-activate" after a latent period, or because they get a new infection from an external source.
A team of researchers at the Pohang University of Science and Technology in Kyungbuk, Korea, along with collaborators at the Yonsei University College of Medicine and the International Vaccine Institute in Seoul, wondered if they could develop a therapy that not only knocks out existing TB infections, but protects against the repeat infections that make the disease so problematic. Led by Youngchul Sung, the team engineered a strand of DNA containing two genes from TB and injected it into mice that model chronically sick patients. The aim was to have the genes, Ag85A and PstS-3, stimulate an immune reaction in the infected mice.
An injection of the engineered DNA boosted the efficacy of standard TB drugs: Six of 10 mice that got only drugs showed signs of reactivated infections while none of those receiving the combination treatment did, the researchers report in the 24 March issue of Gene Therapy. A second experiment showed that the drugs-plus-DNA therapy reduced bacterial growth from a secondary infection, and in one of seven animals, it gave "complete protection" to the lungs against reinfection.
The results are encouraging, says immunologist Douglas Lowrie of the National Institute for Medical Research in the United Kingdom, who has worked on DNA vaccines and recently co-developed a fast test for TB. If the method could be made to work for humans, he thinks it would be "relatively easy" to scale up development. Other TB experts offer two caveats: this experiment was not large enough to determine whether mice were protected specifically by the injected DNA or by a generalized immune response, and other DNA vaccines have not been efficacious so far in human trials.