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Nose-spray vaccine against botulism effective in first tests
Date:1/8/2009

and extremities, inhibiting their ability to release of the neurotransmitter acetylcholine and causing paralysis. In an important 1995 discovery, John Middlebrook, Ph.D., of the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), found that Hc50 fragment of BoNTs, unlike the whole toxin used in the current vaccine, are not toxic when detached from the rest of the toxin, but still bring about the desired immune response.

To insert Hc50 and prime the immune system against it, researchers took a page from gene therapy, which uses disabled viruses as delivery vehicles into cells. Viruses are precision-designed by nature to invade cells and deliver therapeutic genes, and can do so safely once the viruses' own reproductive genes have been removed. Past studies have shown that adenoviruses expressing protein antigens can be delivered by the mucosal route. In addition, adenoviruses can be quickly and inexpensively mass produced, making them an attractive platform for researchers currently developing vaccines against HIV, bird flu, tuberculosis and anthrax, as well as against BoNTs. Zeng and colleagues are currently testing a nasal anthrax vaccine as well.

In the current study, the team used the virus to deliver BoNT/C Hc50 as a mucosal vaccine against botulism in a mouse model. A single dose of intranasal inoculation (nose spray) of the adenovirus vector brought about a high level of HC50-specific immune response as early as two weeks after vaccination. The response consisted of the activation of antibodies, immune cells in both mice and humans that attach to bacterial proteins like BoNTs to shut down their toxic effect. Antibodies classes start with the "Ig" prefix standing for immunoglobulin, another name for antibody, and the specific response to vaccine in the current study consisted of IgG, IgG1, and IgG2a activation in the blood and IgA activation in mucous membranes.

In mice injected with lethal doses of BoNT/C toxi
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Contact: Greg Williams
Greg_Williams@urmc.rochester.edu
585-273-1757
University of Rochester Medical Center
Source:Eurekalert

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