Oral intake of allergens or auto-antigens via the lactic acid bacterium Lactococcus lactis might be a new strategy for treating various kinds of auto-immune and allergic disorders. VIB researchers associated with Ghent University, in collaboration with the Academic Medical Center (AMC) in Amsterdam, have shown that auto-antigens or allergens can be administered orally via the lactic acid bacterium. Based on this principle, which has been patented by VIB, ActoGeniX − a spin-off from VIB and Ghent University − is already developing a variety of biopharmaceutical medicines for a range of clinical indications.
The immune system
Every day our immune system combats harmful substances and micro-organisms that seek to penetrate our body. However, if our immune system is not working properly, we are subject to a variety of diseases. In the case of auto-immune diseases, the immune system no longer distinguishes between our body’s own substances and foreign substances and begins to attack our own tissues and organs. In other cases, the immune system responds mistakenly to harmless substances, such as the house dust mite, milk products, or pollen. This inappropriate immune system reaction to contact with such substances (allergens) is called an allergy. Today, 20% of the European population suffers from an allergy, which is twice as many sufferers compared to 15 years ago.
Lactococcus as supplier of remedies
In its natural form, the lactic acid bacterium (Lactococcus lactis) is a well-known food bacterium that has been used since time immemorial to convert milk into cheese and yoghurt. In the battle against chronic intestinal diseases, VIB researchers have been using L. lactis as a producer of a drug against gastroenteritis. The initial results of the clinical trials are promising.
Now, the bacterium is also being used to fight other disorders. There are a number of active substances for the treatment of allergies and auto-immune diseases that scientists suspect are effective in suppressing these diseases. However, it seems to be impossible to introduce these substances into the intestine in an effective manner. Pieter Rottiers and his VIB colleagues came up with the idea of calling on L. lactis once again. They introduced DNA with the code for a therapeutic protein into the bacterium’s DNA. Together with Inge L. Huibregtse, a physician at the AMC, the VIB researchers succeeded in having L. lactis produce the ovalbumin (OVA) protein.
Tested on mice
Inge L. Huibregtse (AMC) and Veerle Snoeck (VIB) evaluated the use of OVA-secreting bacteria on mice that were allergic to ovalbumin. By administering OVA-secreting bacteria, which deliver ovalbumin to the right place in the intestine, they succeeded in creating ovalbumin-tolerant mice.
This research demonstrates that L. lactis can be employed to induce tolerance toward certain substances. This innovative strategy can now be developed further for the treatment of allergic and auto-immune disorders. The rising incidence of these disorders calls for more effective treatments with fewer side effects. The biopharmaceutical company ActoGeniX is playing a crucial role in the development of such new medicines. Indeed, upon its founding in 2006, ActoGeniX acquired the complete patent portfolio concerning this technology from VIB and Ghent University. ActoGeniX is now using this technology to develop a series of safe, effective medicines in a broad spectrum of disease areas.
Relevant scientific publications
This research appears in the authoritative journal Gastroenterology (Huibregtse et al., Induction of OVA-specific tolerance by oral administration of Lactococcus lactis secreting OVA, Gastroenterology, 2007). Other informative publications that preceded this research:
Braat et al., Clinical Gastroenterology and Hepatology, 4, 754-759 (2006)
Vandenbroucke et al., Gastroenterology, 127, 502-513 (2004)
Steidler et al., Nature Biotechnology, 21, 785-789 (2003)
This research has been funded by UGent and VIB.