NEW YORK (Reuters Health) - A double-gene DNA vaccine combined with conventional antibiotic treatment blocks tuberculosis reactivation and protects against secondary infection in mice, a South Korea research team reports. These results are “pretty remarkable,” commentator Dr. Douglas B. Lowrie told Reuters Health.
“TB is a problem because the immune system can only go so far on its own, failing to eliminate bacterial infection in a significant proportion of the population,” explained Dr. Lowrie, who is based at the National Institute for Medical Research in London.
“Even when patients with TB are treated with drugs, they can be reinfected because they don’t acquire lifelong solid immunity against reinfection,” he continued. “Multiple infections are a problem in areas of the world where there is a lot TB, so it is significant that by giving antimicrobial drugs plus a DNA vaccine, we can reduce the likelihood of that happening.”
For their vaccine, Dr. Youngchul Sung at Pohang University of Science and Technology, in the Republic of Korea, and colleagues chose two Mycobacterium tuberculosis antigens -- Ag85A and PstS-3 -- expressed on infected macrophages at different phases of infection.
Four weeks after infection with M. tuberculosis, mice were treated with isoniazid and pyrazinamide for three months. During this time, the animals were vaccinated five times with empty DNA, Ag85A DNA, PstS-3 DNA, or a combination of both genes.
Following treatment with dexamethasone, 6 of 10 animals receiving antimicrobial treatment alone exhibited infection reactivation. Reactivation did not occur in any of the DNA-vaccinated animals, the team reports in the February 3rd online issue of Gene Therapy.
All three DNA vaccines induced strong antigen-specific interferon-gamma responses, “indicating that coimmunization of DNA plasmids encoding two different antigens did not interfere with each other in inducing interferon-gamma immune response specific for each antigen,” the investigators write.
The animals were then reinfected at 66 weeks after primary infection and bacterial numbers were determined 4 weeks later. Compared with the other three groups of mice, only those given the double-gene vaccine exhibited significantly reduced bacterial numbers in the lung and spleen, suggesting a synergistic effect of multigene DNA vaccination.
The success of Dr. Sung’s team also “offers encouragement” that DNA vaccines could perhaps be used for primary prevention, Dr. Lowrie added.
Source: Gene Ther 2005. [ Google search on this article ]
MeSH Headings:Recombinant Proteins: Vaccines, Synthetic: Vaccines, DNACopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
