“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 and comprehensive immune response in immunized mice. “These findings suggest that plasmid DNA vaccination could potentially be made more effective in larger animals and humans by coupling the vaccine to a heterologous DNA sequence, which is highly expressed in mammalian cells,” says Brannon.
This work was supported in part by grants from the National Institutes of Health.
This release is a summary of a presentation from the 102nd General Meeting of the American Society for Microbiology, May 19-23, 2002, in Salt Lake City, Utah. Additional information on these and other presentations at the 102nd ASM General Meeting can be found online at http://www.asmusa.org/pcsrc/gm2002/presskit.htm or by contacting Jim Sliwa (jsliwa@asmusa.org) in the ASM Office of Communications. The phone number for the General Meeting Press Room is (801) 534-4720 and will be active from 10:00 a.m. MDT, May 19 until 12:00 noon MDT, May 23.