Checkbiotech.org

Although the plague, also called the Black Death, has lost most of the fear it caused in medieval times, it is still endemic in Southeast Asia, Southwest USA and some parts of Africa. The most life threatening form of the disease is pneumonic plague, which can either develop from a fast-developing bubonic plague, or arise by direct infection of the lungs. It is highly contagious because it can spread rapidly from person to person by air, thereby killing a healthy person within three or four days. For these reasons, the worry has arisen that Y. pestis, the etiologic agent of the plague, might be used as a biological weapon.

Should a bio-attack with pneumonic plague occur, currently there is no safe and efficient plague vaccine available. Production of vaccines consisting of whole, killed bacteria was stopped due to inefficiency against pneumonic plague and high incidence of side effects, and new vaccines are still in development. Strategies for improved plague vaccines are based on using “subunit vaccines”. This means that specifically only two proteins from Y.pestis known to provoke a strong immune response are used; these are the so-called F1 and V antigens.

Thus the goal of Dr. Alvarez and her colleagues is to produce the perfect vaccine against the plague – easy to administer, safe, efficient and inexpensive – in particular against the pneumonic form. Currently, they have developed a transgenic tomato plant, which is capable of producing a F1-V fusion antigen in amounts up to 10% of the total plant proteins. These F1-V tomatoes are then the raw material for vaccine production and are freeze dried for long term storage. This system can easily be scaled up if there is a high demand, for example to protect people from biowarfare. In addition, they proved that the edible vaccine provokes an immune response which consists of the production of specific antibodies against the F1-V antigen if the transgenic tomatoes are fed to mice.

The researchers speculate that the vaccine is effective, because being that the tomatoes are freeze-dried, the antigen is protected from degradation in the stomach by the plant cell wall. This allows the antigen to reach the lymphoid tissue in the gut where it elicits the immune response. Edible vaccines are a very convenient way to deliver a vaccine, because they eliminate the need for costly purification of the antigen and formulation of pills for efficient oral delivery.

“Of course, the final goal of our plague-vaccine project is to develop an exclusively oral tomato vaccine, using only tomatoes from second generation plants, which contain a higher concentration of the F1-V antigen,” says M. Lucrecia Alvarez.

The next step would obviously be to expose mice to pathogenic bacteria to test whether the elevated levels of antibodies correspond to increased resistance to Y. pestis bacteria. This work is already underway at the National Wildlife Health Center in Madison, Wisconsin. In the preliminary results, mice were injected subcutaneously with bacterially derived F1-V, and boosted with transgenic tomato were protected against exposure to Y. pestis.

At the moment, six human trials have been carried out using plant derived vaccines for different diseases, and as Dr. Alvarez speculates, “The plague vaccine produced in tomatoes might be ready for clinical trials on humans in less than two years, but of course, it all depends on the results of our future animal trials.”

“In addition, we also plan to use the F1-V tomatoes to vaccinate animals as well, since they act as reservoirs of plague in regions where the disease is endemic. For that reason, we initiated collaboration with the laboratory of Dr. Rocke at the Wildlife Health Center.”

With these results, the Cardineau lab is already a step closer to the goal of producing an easy to deliver and economic plague vaccine.

Daniela Kenzelmann is a Science Journalist for Checkbiotech and is writing her PhD at the Friedrich Miescher Institute in Basel, Switzerland. Contact her at daniela.kenzelmann@fmi.ch

Alvarez ML et al. Plant-made subunit vaccine against pneumonic and bubonic plague is orally immunogenic in mice. Vaccine, 2006 Mar 24;24(14):2477-90

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