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 www.Checkbiotech.org