Researchers use self-destructing salmonella to deliver oral DNA vaccines

Researchers at Arizona State University's Biodesign Institute have taken salmonella, a potentially deadly bacterium, and turned it into a safe and efficient way to deliver DNA vaccines by mouth, with the added advantage of much lower manufacturing costs, too. In the U.K., this would be described as "poacher turned gamekeeper."

The team has engineered a salmonella bug to get into cells quickly and efficiently without killing the cells and then self-destruct, releasing the DNA, which then hijacks the cell's manufacturing abilities to synthesize the antigens. According to Roy Curtiss, director of the Center for Infectious Diseases and Vaccinology at the Biodesign Institute, this could be used against any virus, any parasite, or any fungus.

"Here, we were able to deliver a vaccine whose DNA sequence induces the immunized individual to make the protective glycoprotein the way you would during a viral infection," Curtiss says.

To check that the idea worked, the team created a vaccine that protected mice against a lethal dose of flu virus and was safe in newborn, pregnant and immunodeficient mice. The research is published online in Proceedings of the National Academy of Sciences. One of the team's vaccines is in Phase I clinical trials against infant pneumonia.

Because these vaccines, known as RASVs (recombinant attenuated salmonella vaccines), are live, they trigger a better immune response than killed vaccines, but one of the concerns is that they will cause disease or escape into the environment. The team has worked around this by engineering the bugs to implode if they can't find a certain type of sugar, one that does not occur naturally. This is tailored to give the bacteria time to get into the cells and synthesize the antigens to trigger an immune response.

The added advantage of the technique is that the vaccines can be manufactured quickly and cheaply, freeze-dried and stockpiled, allowing fast response to pandemics or bioterrorism. As Curtiss' colleague Wei Kong says: "By delivering the DNA vaccine using a recombinant attenuated bacterium, we can get 10,000 to 100,000 doses per liter of culture." This is much faster than existing techniques such as isolating DNA from bacteria before injection.

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