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"DNA vaccines represent a bold new way to immunize humans against infectious diseases," said company president, Clague Hodgson, "However, their effectiveness up to the present has been borderline, and the science requires quantum forward leaps in both efficacy and production in order to reach practicality."

NTC scientists Jim Williams and Aaron Carnes headed up the studies at the company's facilities located in the University of Nebraska Technology Park in Lincoln, NE. Using NTC's Gene Self-Assembly (GENSA) combinatorial technology, Williams and his colleagues quickly optimized many components of the DNA vaccine backbone, reducing its size by 40%, increasing both the potency and the vaccine's ability to express antigens at comparatively higher levels in both cell culture and animal models. By expressing the antigen genes via a number of different pathways in so-called mixed-mode presentation using NTC's DNAVaccUltra vaccine system, it is possible to boost exposure of the host's immune system to the foreign proteins.

An advantage of DNA vaccines is the ability to safely expose humans to antigenic DNA molecules in the absence of traditional (weakened or killed) pathogens, such as viruses or bacteria. However, in addition to effectiveness, the vaccine must be produced in great quantities and at a reasonable cost of no more than a few dollars per injection.

The team led by NTC scientist Aaron Carnes produced stunning gains in productivity by increasing the actual yields of the DNA vaccines (or DNA plasmids) that can be obtained from bacterial fermentation, the process used to manufacture DNA in large quantities. "Just a few years ago, we were happy to obtain a hundred milligrams per liter," Carnes said, emphasizing, "Now, it is possible to obtain improved yields of over a gram per liter, and we continue to see gains as we learn more about the upstream fermentation process."

Convinced that more improvements will be made, Williams and NTC recently obtained two Small Business Innovation Research (SBIR) awards from the National Institutes of Health, funding ongoing work aimed at streamlining the vaccine production process through genetic engineering of the bacteria that make the DNA. This approach is designed to turn the bacteria into programmable factories, both for growing, and for processing, large quantities of vaccine DNA, according to Williams.

According to Hodgson, an advantage of the team's approach of developing both efficacy and production at the same time is that it allows collaboration with industry and academic researchers with strong antigens against diseases such as HIV-AIDS, hepatitis B and C, influenza, SARS and smallpox. "The best collaborations in this regard can potentially move quickly through the clinic and into production, using NTC's RapidVACC fast deployment system," he said, emphasizing that time is of the essence in moving against imminent biological threats.

NTC is a development stage biotechnology company, focusing on genetic vector technology.