Almost half of the world population is infected with bacteria Helicobacter pylori which colonizes stomach, causing gastritis and ulcers and is recognized by WHO as a type I carcinogen. Current antibacterial treatment, implemented after the seminal discovery that H. pylori infection is the underlying cause of ulcers, which brought the discoverers the Nobel Prize in 2005, requires combination of at least three different drugs to eliminate bacteria.
However, it does not prevent reinfection, which often occurs within the family. Additionally, bacterial resistance decreases the efficiency of therapy. Effective vaccine against Helicobacter pylori is not available, although it could be a durable solution, particularly in a formulation affordable to the third world population.
Helicobacter is able to withstand the harsh environment of stomach and avoids immune recognition by making itself invisible to the cellular receptors by modifying several of its components such as those of the flagella, which it uses to propel within the lining of stomach and duodenum.
Team of undergraduate students of the University of Ljubljana, led by their mentors from the National institute of chemistry and University reported on the research project, aimed at preparing a hi-tech vaccine against Helicobacter. Their strategy was to modify the flagellin of Helicobacter pylori by transplanting segments of flagellin from another bacterium, which is able to efficiently activate cellular immune receptors. They managed to demonstrate that this type of modification makes flagellin of Helicobacter visible to the immune system.
To increase the efficiency of immune response they added several segments of most important virulence factors of Helicobacter pylori to a synthetic vaccine. They prepared three different implementations of vaccine, including isolated proteins, DNA vaccine and modified bacteria that present polypeptides of Helicobacter at their surface. “We think that bacteria might be easiest to implement as the vaccine in remote areas, because you could just reconstitute lyophilized bacteria or bacterial ghosts, provided that the oral or mucosal vaccination would show adequate efficiency”, is optimistic Jerneja Mori, fourth grade student of microbiology at the Biotechnical faculty.
Project was accomplished in five months from the idea to the demonstration of the proof of concept and was prepared as entry for the International Genetically Engineered Machines Competition (iGEM) held each year at MIT, Cambridge, USA. This year 84 teams from 21 countries including world’s best universities competed with their projects in synthetic biology. Six finalists (Slovenia, Harvard, Caltech, Freiburg, UC Berkeley and NYMU Taipei) presented their project to all participants and judges, coming from academia, biotech, pharmaceutical and science publishing companies. Slovenian teams had a row of successes at this competition, qualifying each time in the last three years among the finalists. This year their project was selected as the best in the track “Health and Medicine” and they also won the Grand Prize award in overall ranking.
Team leader prof. Roman Jerala, head of the Department of Biotechnology at the National institute of Chemistry explains: “I had some doubts whether it will be possible to demonstrate the proof of principle within such a short time. Nevertheless, students were extremely motivated and we were able to demonstrate activation of immune receptors and response in vivo against the proteins of Helicobacter pylori”. “Before we can state that vaccine is truly effective, we have to do much more work but current results are quite encouraging”, is optimistic mentor prof. Simon Horvat from the Biotechnical Faculty of the University of Ljubljana.
In addition to modified flagellin, Slovenian team proposed another approach which involved modifications of the signaling network of innate immune receptors. The power of this approach is that we can mimic synergistic activation of several TLRs by pathogenic microbes, while having the advantage of safety of a defined subunit vaccine. They have already filed two patent applications and are determined to continue to complete all the tests of the therapeutic efficiency of vaccine. “The ultimate goal would be to prepare a vaccine to eradicate Helicobacter pylori”, says Jan Lonzaric, student of biochemistry, who successfully presented the project at the competition.
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