Foreign DNA makes TB vaccine better

SALT LAKE CITY May 23, 2002 -- An experimental DNA vaccine against tuberculosis appears to be significantly improved by the addition of DNA from a completely unrelated organism, say researchers from the Corixa Corporation in Seattle. They report their findings today at the 102nd General Meeting of the American Society for Microbiology.

Vaccination with plasmid DNA designed to produce a particular protein(s) for presentation by the immune system is a promising method for generating immunity and protection against infectious diseases and cancer. Currently, while this method of vaccine delivery works well in mice, it has proven to be a challenge in both non-human primate and human studies. One of the reasons DNA vaccination has not been effective in humans or in primate models may be due to the low amount of protein produced, or, put another way, the high amounts of DNA needed to stimulate immune responses. We have recently found ways to greatly increase DNA vaccine efficiency by including sequences that enhance protein production in vivo, says Dr. Mark Brannon, one of the study researchers.

Brannon and his colleagues studied a Mycobacterium tuberculosis antigen, known as Mtb 8.4, that has shown promise as a TB vaccine based on the immune responses generated in vaccinated mice.

Experiments have suggested that the Mtb 8.4 DNA vaccine might not produce sufficient protein to be useful in non-human primate studies. We reasoned that the amount of Mtb 8.4 protein produced in a DNA vaccine format could be considerably increased by fusion to a gene known to express a high level of protein in eukaryotic model systems, says Brannon.

The gene they chose expressed the thiol-specific-antioxidant (TSA) protein from Leishmania major. Transfection of mammalian cells with the hybrid DNA vaccine resulted in a considerable increase in the protein expression level of Mtb8.4. The increased amount of Mtb 8.4 protein generated by the fusion resulted in a more robust a

Contact: Jim Sliwa
American Society for Microbiology

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