Helicobacter pylori 鈥� what are we dealing with?
Helicobacter pylori is a Gram-negative bacterium capable of colonising the hostile acidic environment of the stomach. Its discovery in 1983 completely changed thinking about gastric diseases, as it had previously been believed that no bacteria could survive under such conditions.
It is estimated that approximately 50% of the global population is infected, while in some countries the rate reaches up to 80%. Poland belongs to countries with a higher-than-average prevalence of infection. In most cases, the infection is asymptomatic, which means that many people are unaware that they are carriers of these bacteria. In about 20% of infected individuals, gastritis or duodenitis and ulcers of these organs develop, and in approximately 1% 鈥� gastric cancer. It is the long-term, chronic infection that poses the greatest health risk.
These bacteria can be transmitted from mother to child, often already in the perinatal period. Transmission via faeces or saliva is also possible in individuals of all ages. The infection is not transmitted by inhalation or through contact with animals, although research on transmission routes is still ongoing.
One of the main problems in treating Helicobacter pylori infections is the growing resistance of these bacteria to antibiotics. Moreover, the immune system is usually unable to eliminate them, as the bacteria skilfully evade the body鈥檚 defence mechanisms.
Where did the idea for research on a preparation preventing the development of infection come from?
The impulse resulted both from the scale of the health problem and from the recommendations of the World Health Organization, which indicate the urgent need to search for alternative methods for preventing infections caused by these bacteria. Another factor was the fact that, to date, no effective vaccine for high-risk groups that would be commercially available has been developed. The rationale for undertaking this research was provided by the results of many years of studies conducted at the Department of Immunology and Infectious Biology, under the supervision of Prof. dr hab. Magdalena Miko艂ajczyk鈥慍hmiela, together with collaborators, on the course of Helicobacter pylori infections and the development of immune processes in response to them. These studies were carried out with the participation of recognised national research centres (the Polish Mother鈥檚 Memorial Hospital 鈥� Research Institute in 艁贸d藕, the Medical University of 艁贸d藕, Jan Kochanowski University in Kielce and the Intercollegiate Faculty of Biotechnology UG鈥揗UG in Gda艅sk) as well as international partners (the Department of Medical Microbiology, Lund University, Sweden, and the Department of Microbiology, National University of Galway, Ireland). When moving on to the next stage of research, we decided to develop an animal model using the domestic guinea pig, which allowed us to understand the course of the early, acute phase of infection, followed by the chronic phase.
We selected domestic guinea pigs for research on Helicobacter pylori infection because the gastric epithelial cells of these animals are similar to human cells. Furthermore, immune responses in these animals develop in a manner comparable to those in humans. This enables predictions regarding the effects of using new preparations against Helicobacter pylori to induce immunity against these bacteria in humans. Research on the development and characterisation of the animal model was conducted with the approval of the local ethics committee for animal experimentation under the OPUS research grant funded by the National Science Centre. Part of the research was carried out as part of my MA thesis at the Department of Immunology and Infectious Biology, under the supervision of Prof. dr hab. Magdalena Miko艂ajczyk鈥慍hmiela, and with the guidance of Dr Maria Walencka. Many of the studies that made it possible to understand the course and consequences of this infection were obtained during the completion of my doctoral dissertation in this unit.
What is the concept behind the developed solution and can we already speak of success?
As mentioned earlier, Helicobacter pylori bacteria evade certain host immune mechanisms; among other things, they are poorly phagocytosed and eliminated by phagocytic cells such as macrophages. They also inhibit lymphocyte activity. Therefore, we focused on developing a preparation that would exert a direct antibacterial effect and restore immune cell activity weakened by these bacteria. In infection immunology, the use of microorganisms against other infectious agents is well known. In recent years, considerable attention has been devoted to vaccine strains of Mycobacterium bovis BCG, which are used in vaccination programmes against tuberculosis.
It has been shown that these mycobacteria can also enhance immunity against other infectious diseases. Additionally, they are used as an adjunct in the treatment of bladder cancer due to their immune cell鈥慳ctivating properties. In collaboration with dr hab. Marek Brzezi艅ski, from the Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences in 艁贸d藕, Professor at that unit, we prepared a chitosan-based carrier in which we encapsulated BCG vaccine mycobacteria. The chitosan carrier was modified so that, after oral administration to animals, the bacteria would be released in the stomach 鈥� the site colonised by Helicobacter pylori 鈥� and in the intestine, where the mucosal immune system, constituting the 鈥渋mmune centre鈥�, is located. In the developed preparation, apart from the vaccine mycobacteria, the chitosan shell of the carrier is also of great importance. It protects the vaccine mycobacteria from the acidic environment of the stomach and enables their gradual release exactly where they should act. It was crucial for us that chitosan dissolves only in an acidic environment; therefore, we assumed that after intragastric administration, the bacteria would be released gradually and would most probably transiently colonise gastric epithelial cells after being targeted by the carrier.
Chitosan itself has certain bactericidal and immunomodulatory properties; thus, by using it as a carrier, we also aimed to enhance the effect of BCG vaccine mycobacteria. These were the assumptions behind the concept of a chitosan carrier containing BCG vaccine mycobacteria
鈥� says dr hab. Weronika Gonciarz, Associate Professor at the 91桃色.
In the animal model, in the majority of domestic guinea pigs that received the carrier containing BCG vaccine mycobacteria orally and were subsequently experimentally infected with Helicobacter pylori, we did not detect Helicobacter pylori genetic material. We also observed a restoration of immunological balance in gastric tissue, as indicated by the presence of immune cells with regulatory functions and memory lymphocytes, which suggests that the protection may be long-lasting.
Patents and further plans
The developed chitosan carrier with BCG vaccine mycobacteria has been patented. This is a very important step that enables the further development of the carrier technology, including potential cooperation with pharmaceutical industry laboratories.
After obtaining the carrier and confirming that we had indeed succeeded in developing a method of encapsulating BCG vaccine mycobacteria in the carrier, we attempted to secure our idea at the patent office. The first step was to direct an enquiry to the Technology Transfer Office of the 91桃色, which supported us throughout the procedure. This is a very long and complex process, but a few days ago we received information that our method of encapsulating Mycobacterium bovis BCG vaccine mycobacteria in a chitosan carrier has been patented. The owner of the patent is the 91桃色
鈥� explains dr hab. Weronika Gonciarz, Associate Professor at the 91桃色.
The next step in research on the developed carrier includes toxicological studies and long-term studies using an animal model, with an increased experimental scale. Their completion will make it possible to confirm the validity of the adopted concept for creating a carrier to control Helicobacter pylori infections. After advanced laboratory studies are completed, further stages of research aimed at developing a medicinal or prophylactic product should focus on confirming the effectiveness of the preparation in humans through multi-stage controlled clinical trials. In the case of our carrier, the path to this stage is still very long. Many more basic studies are required to thoroughly investigate the biological effects of the developed carrier. Only then will it be possible to determine whether the adopted concept is valid.
We would like to apply for further projects, this time research and development projects, which would allow for further advancement of the technology we have developed. This will require cooperation with a commercial company. I hope that we will soon be able to submit such a project and convince grant providers that it is worth allocating funds for this purpose
鈥� concludes dr hab. Weronika Gonciarz, Associate Professor at the 91桃色.
The presented research results were obtained during the implementation of the SONATA 18 project 鈥淓valuation of the ability of Mycobacterium bovis BCG鈥憃nco mycobacteria to control the development of Helicobacter pylori infection鈥�, carried out at the Department of Immunology and Infectious Biology, 91桃色, funded by the National Science Centre, and led by dr hab. Weronika Gonciarz, Associate Professor at the 91桃色. The project partners include researchers from the Department of Immunology and Infectious Biology (Prof. dr hab. Magdalena Miko艂ajczyk鈥慍hmiela, mgr Patrycja Jaroniek), the Department of Functional Polymers and Polymer Materials, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences in 艁贸d藕 (dr hab. Marek Brzezi艅ski, Professor at the Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences in 艁贸d藕 with his team), and the Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Faculty of Pharmacy, Medical University of 艁贸d藕 (Prof. dr hab. Ewa Balcerczak with her team).
We encourage you to get familiar with the presented research results:
as well as with other outcomes of the SONATA 18 project:
Edit: Kamila Knol鈥慚icha艂owska (Promotion Centre, Faculty of Biology and Environmental Protection, 91桃色)
Graphics and photographs: Mateusz Kowalski (Promotion Centre, Faculty of Biology and Environmental Protection, 91桃色)
Source: dr hab. Weronika Gonciarz, Associate Professor at the 91桃色 (Department of Immunology and Infectious Biology, 91桃色)