Bacteria vs bacteria: edible vaccines

Bacillus subtilis, or hay bacillus, is one of the best-characterized Gram-positive bacteria in molecular biology research. This environmental species, also present in the human digestive tract, is commonly used as a component of probiotics. This bacterium has fully sequenced genome and is naturally competent, which means the ability to accept foreign genetic material by transformation. The ease of genetic manipulation enables to utilize it for the production of different types of proteins originating from other organisms. Another feature of B. subtilis is the ability to form spores, which is a physiological process triggered in response to adverse environmental conditions. Spores are the most durable cell structures produced by living organisms on Earth. They are able to survive high temperatures, extreme pressure, space vacuum, UV radiation, and potentially even a meteorite strike.
 

Polish-Italian team

Researchers from the Department of Molecular Bacteriology, Intercollegiate Faculty of Biotechnology UG&MUG for several years work on the use of B. subtilis spores as carriers of antigens of human pathogens such as Helicobacter pylori and Clostridium difficile. For ten years, the Polish team closely cooperates with prof. Ezio Ricca from the Department of Biology at the Federico II University of Naples, which is one of the world leaders in the use of B. subtilis spores as carriers (i.e. of tetanus toxin and rotavirus proteins). The Italian team also specializes in the study of the structure and composition of the outer spore coat, where the heterologous proteins are directly exposed. Currently ongoing twinning, thus the two-way secondments of reserachers, is financed under the project MOBI4Health (7th EU Framework Programme), which aims to increase the potential of the Intercollegiate Faculty of Biotechnology UG&MUG in the field of molecular biotechnology. Federico II University of Naples is one of the ten European partners of IFB within the project. What especially an international cooperation provides? - A big part of research work does not end successfully, by means of an article in a scientific journal. The access to “unpublished” knowledge is as important as access to libraries – responds the Head of the Department of Molecular Bacteriology, Prof. Michał Obuchowski.

Benefits, benefits, benefits...

Thanks to their properties, B. subtilis spores seem to be the ideal carrier of potential antigens for immunization. Such specimens are resistant to digestion, which enables an oral administration. The powder or tablet could be simply swallowed, which is a good news for people who do not enjoy injections and also there is no need to provide aseptic environment during administration. Spores do not require special storage conditions, which may be important in case of transport to distant locations, disaster areas and third world countries. This positively affect the cost of storage and transport. The whole process of production (culture), in fact, is based solely on the ability to achieve physiological stage of dormant metabolism, which can be triggered simply by depletion of nutrients in the culture medium.

Close enough to success?

Projects implemented so far in the Department of Molecular Bacteriology helped to create a system of vectors enabling quick and easy creation of fusion proteins for the surface presentation (Tavassoli 2013; Hinc 2013; Negri 2013; Iwanicki 2014; Hinc 2014). The first Polish patent for the use of spores in the vaccination against H. pylori was granted in 2014, another are pending. A streak of success is unfortunately not free from difficulties encountered. The first work describing the subject appeared in the late 90s of last century. Therefore, the idea is not new, which is a challenge in the pervasive requirement for innovation. - We are now trying to raise funds to continue this path of research - says Prof. Michał Obuchowski. - This can be compared to climbing: the number of mountains on Earth is limited, and yet we still have reports of entering a new road or other conditions, and this is considered as a novelty. This methodology is similar. Each protein has its own unique characteristics which is challenging for the researcher wishing to expose it on the spore surface.

Another difficulties are of legislation nature, because the sporulating bacteria presenting foreign antigens are, in accordance with applicable law, genetically modified organisms. Prof. Obuchowski, however, is an optimist. – The atmosphere surrounding GMO is similar to the situation that took place during the introduction of the railroad. There were also famous academics who claimed that just watching the fast train in motion may cause conjunctivitis. Over time, the public accepted the existence of railways, and so it will be for GM organisms. Unfortunately, nobody will give us back the time lost by impractical regulations.

Monika Kossakowska-Zwierucho