www.czu.cz ; www.raupp.info

Recently many politicians in the US and the EU have received Anthrax-laced
envelopes. The threat of biological warfare and terrorism is real; Anthrax
is just one of many potential bio attack agents, but it is a serious one.
Since the only vaccine existing so far against Anthrax has some
disadvantages, researchers are now developing a new one, December 2004 by
Katharina Schoebi, Checkbiotech .

Anthrax is endemic in the US and is caused by the bacterium Bacillus
anthracis that infects humans in one of three ways: through the skin
(cutaneous anthrax), through consumption of contaminated meat products
(gastrointenstinal anthrax) and through the nasopharynx (inhalational
anthrax). However, once in the human body the bacteria produce toxins that
lead to symptoms and possible death.

The Centers for Disease Control (CDC) lists anthrax as a category A disease
agent with easy dissemination or transmission, high mortality, social
disruption and a special preparation needed. Nowadays, biological warfare
and terrorism is a real threat. The CDC estimates that the cost of an
anthrax attack would be US$ 26.2 billion per 100,000 persons exposed!

The only vaccine licensed so far for human use in the US is Biothrax, which
unfortunately has some disadvantages: it has to be injected several times,
causes local reactions at the site of the subcutaneous injection and could
also lead to side-effects in some individuals. Therefore, researchers are
looking for ways, by which they could produce a new vaccine on a large scale
and at reasonable cost.

An economical and convenient way to obtain pharmaceutical products, without
human or animal pathogen contamination, is to let plants produce them. In
plants, not only the nucleus contains DNA but also the chloroplasts.
Chloroplasts are the organelles the plant needs for the photosynthesis.
Since they are very advantageous for genetic engineering, they are often
used in plant science experiments. If you insert a gene of interest in the
DNA of the chloroplasts, you will have two copies of that gene when the
chloroplasts divide (when the plant is growing). Bearing in mind that there
are up to 10,000 copies of chloroplast genomes per cell, you will obtain
quite a large amount of the gene of interest by cultivating plants.

One disadvantage of producing pharmaceutical proteins in plants is the
possibility of plant-based pharmaceuticals mixing with food supplies. To
prevent this, scientists have turned to producing the pharmaceutical
products in non-food or feed crops such as tobacco (Nicotiana tabacum).
Tobacco is an often used plant in biological experiments, because it has
many advantages: It is a self-pollinating crop with up to one million seeds
per plant, it can produce a large amount of biomass (more than 40 t fresh
leaf weight/acre), it has no known wild or cultivated relatives in North
America and it is easy to enhance through genetic engineering. By harvesting
tobacco leaves before the onset of flowering, the possible flow of genetic
material via pollen or seed is eliminated and the contamination of food
crops is prevented. In addition, there exists a large-scale processing
infrastructure.

Two researcher teams headed by Henry Daniell from the Department of
Molecular Biology and Microbiology at the University of Central Florida in
Orlando, USA, and Stephen H. Leppla from the Microbial Pathogenesis Section
at the National Institute of Allergy and Infectious Diseases, produced the
Bacillus anthracis protective antigen (PA) in chloroplasts of tobacco.

In their experimental studies, they obtained a total of 172 mg of full
functional PA from each plant. Extrapolating that out, that would mean that
about 8,000 tobacco plants could be grown in an area of one acre. Each year
a total amount of 4.12 kg of PA could be expected, out of which 50% would be
lost during purification. Taking into consideration that about 5 ?g PA are
used per dose of the vaccine, researchers could produce about 400 million
doses of vaccine per acre of tobacco. That number might jump to well over 3
billion vaccines, when a commercial tobacco variety is used, in the place of
the laboratory variety that Dr. Daniell and Dr. Leppla used.

Having produced the new antigen, the two research teams then had to test its
ability to be used as an effective vaccine. This was determined by its
ability to cause lysis of cultured mouse macrophages, which is a first step
that immunologists use to determine whether or not a vaccine will work or
not. Thus the two research teams headed by Dr. Daniell and Dr. Leppla showed
that the tobacco plants can be used to produced fully functional antigen,
that can then be used as a human vaccine.

Equally important is the longevity of a vaccine. It is often very beneficial
to have a vaccine that can be prepared in advance, and stored until it is
needed. Dr. Daniell and Dr. Leppla were also able to show that there is no
degradation of the PA vaccine upon storage and transportation, which further
points to their PA from tobacco plants as a very favorable Anthrax vaccine.

However, before using the new Anthrax vaccine, the laboratories of Dr.
Daniell and Leppla will have to carry out some future testing before the
vaccine will ready to used for humans, Thus in the near future, their work
promises to help eliminate the threat of Anthrax with a very safe and
cost-efficient vaccine.

Katharina Schoebi is a biologist and a Science Writer for Checkbiotech
[www.checkbiotech.org];
subtopic_id=2&doc_id=9357

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