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Anthrax has a new nemesis
Thursday, October 18, 2007
By Lukas Herwig, Checkbiotech
When Edward Jenner infected a boy with cowpox in 1796, and by doing so introduced the first modern technique of immunization, he probably never imagined that about 200 years later a plant would be used to produce a vaccine against Anthrax.

From inhalation, ingestion or through a cut on your skin, Anthrax poses a great health risk to humans. "In the United States, Anthrax spores have been used as a bioterrorism weapon which led to the death of a few people. That is why a safe and inexpensive vaccine to defeat this disease or threat is readily needed," added Dr. Henry Daniela from the University of Central Florida.

However, the vaccine must be safe and clean. The current available B. anthracis-derived vaccine is efficient, but due to its production process, it has been associated with dangerous side effects such as: edema, local pain and systemic reactions. In short, it is not very safe.

That is why Dr. Daniell and his team generated a new vaccine with a twist - they used plants. Plants are readily becoming safe and inexpensive vaccine production systems. Moreover, plant-based vaccine production provides another important advantage: less contamination of human pathogens and toxins, which is much safer for human health.

Virulent strains of B. anthracis produce a toxin, encoded by three genes - pagA, lef and cya. Lef encodes lethal factor (LF) and cya, a protein called edema factor (EF). However, pagA the "protective antigen" (PA) has become the main target for vaccine production due to its ability to elicit an immune response.

None of the toxins are thought to be harmful alone. However, PA combined either LF or EF, respectively, forms edema toxin or lethal toxin, giving rise to adverse side effects.

To single out the desired pageA, Dr. Daniell`s group transferred the pageA gene into tobacco chloroplast genome (from leaves of Nicotiana tabacum var. petit Havana).

Different from B. anthracis-derived vaccine, where PA is purified from bacterial supernatant, which also contains traces of EF and LF, pure PA was obtained from the genetically modified tobacco.

After confirmation that the transgenic tobacco leaves produce pure and functional PA, they immunized different groups of mice with partially purified PA and crude plant extract together with an aluminium adjuvant, that helps trigger an immune response. As a control, B. anthracis-derived PA was tested in parallel.

As Dr. Daniell and his team supposed, all of the mice developed immunity and were protected against a full dose of Anthrax toxin that was 15 fold higher than the lethal dose. Such results proved very promising to Dr. Daniell`s lab and strongly suggest a new possibility to produce vaccines in a safer and more inexpensive method.

Dr. Daniell told Checkbiotech, "One acre of land could produce 360 million doses of purified PA vaccine." That would mean only 20 acres would be needed to produce enough Anthrax vaccine for the world`s population.

Ongoing studies in the Daniell laboratory with Cholera toxin B, Interferon IFN-?2B (a viral replication inhibitor) and a receptor mediated oral delivery method in other laboratories have also shown promising results, which all will help fine tune plant-based expression techniques that will one day soon allow researchers to produce plants that can be used as oral vaccines.

When asked about ongoing and future steps, Dr. Daniell told Checkbiotech, "Currently we are advancing a permanent cure for diabetes through oral delivery in human pre-clinical trials."  Their work was able to proceed to the clinical stages due to good result in diabetic mice.


Lukas Herwig is studying biology at the University of Basel and is a Science Writer for Checkbiotech.  l.herwig@stud.unibas.ch

Contact:
Henry Daniell, Ph.D.
Pegasus Professor & Trustee Chair
Technical Founder, Chlorogen Inc.
University of Central Florida
4000 Central Florida Blvd
Dept. Molecular Biology & Microbiology
Biomolecular Science, Bldg # 20, Room 336
Orlando FL 32816-2364
Phone:407-823-0952 (office)
Phone: 407-823-0948/0958 (labs)
Fax:407-823-0956
daniell@mail.ucf.edu
http://pegasus.cc.ucf.edu/~daniell
Source: Checkbiotech
   
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