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Using Self-Destructing Bacteria to Carry a Vaccine

By November 6, 2012

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Researchers at Arizona State University have engineered a stain of Salmonella to act as a delivery mechanism for vaccine antigens. The highly engineered bacterial vaccine was used to protect mice against a lethal influenza virus, but the approach can be generally adapted to produce a strong immune response against almost any pathogen.

Investigators have been working on approaches to use bacteria to deliver viruses for many years. Most disease causing bacteria, such as Salmonella, Listeria, Shigella, and Bacilius, have developed to survive on hostile mucosal surfaces such as the mouth, nose, and gut. In addition, the body is finely tuned to recognize these invaders on these surfaces and trigger a robust immune response.  As a result, if these bacteria can be both weakened, to make them safe, and altered, to include an immune-stimulating antigen, they should make excellent vaccines. A few bacteria in the nose or mouth should generate a strong immune response against the antigen.

The problem with this bacterial vaccine approach, however, is that the bacteria used to carry the vaccine antigen are usually engineered to die quickly after infection. While this weakens the bacterial to make it safe, these short lived bacteria do not stimulate a strong immune response, thus defeating the purpose. The Arizona State University group has been able to work around this problem by producing a strain of Salmonella that are able to survive and proliferate for a while in the host, but are still programmed to die after a couple generations.

The vaccine is designed by adding a gene for the antigen into the specially engineered Salmonella bacteria. The bacteria then make the antigen from the inserted gene, is designed so the bacteria place it on their outside surface.  This way, antibodies can "see" it.  These vaccine-engineered bacteria are then grown in large quantities in the lab, producing hundreds of thousands of doses. Vaccination simply involves a spritz of bacterially laden nasal mist or bit of inoculated liquid. Once the vaccine bacteria are in the nose or mouth, they infect the bodies cells and the immune system responds accordingly, exploiting an effective interaction optimized by millions of years of evolution.

Read more about the approach at in the press release. The article is published in the journal PNAS.

 

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