Food restrictions of allergic patients resolved by a novel type vaccine (NFR 184825)
Allergic reactions to food represent a major and growing medical, social and economic problem worldwide. Up to 6 % of small children and 3 to 4 % of adults have a confirmed allergic reaction to basic foods. Eight types of food account for over 90 % of allergic reactions; milk, eggs, peanuts, tree nuts, fish, shellfish, soy and wheat. The clinical reactions of allergy vary from minor oral reactions with itch and mucosal swelling, to urticaria and angioedema, gastrointestinal symptoms, asthma and anaphylaxis with possible fatal result. In the USA, of the 8% of children who suffer from food allergy, 39% has a history of severe reactions. Food anaphylaxis is now the leading cause of anaphylactic reactions treated in emergency departments in Westernized countries. Food allergy significantly impacts quality of life; in addition to the discomfort and sometimes life-threatening situations that the allergic patients experience, many develop a fear of being exposed to hidden allergens. This fear not seldom causes the patient to put heavy restrictions on food intake, with the risk of malnutrition and the need of treatment by psychologists. This is especially the case in peanut allergy, since patients can get severe allergic reactions on exposure to even trace amounts of peanut, which is often found hidden in foods, and therefore difficult to avoid.
The only way to control of food allergy is merely avoidance of the relevant offending allergen, i.e. no vaccine is available for the treatment of food allergy. For venom and inhalant allergies, and grass and birch in particular, desensitization and tolerance development has been carried out more than 100 years as subcutaneous or recently sub-lingual immunotherapy (SCIT and SLIT, respectively) . Treatment involves increasing doses of standardized allergen extracts until a maintenance dose is reached; this dose is injected approximately every second month for 3-5 years. Alternative strategies are currently being tried out, such as intra-lymphatic injections, which may considerably shorten the time of treatment, but such treatment is experimental at present . Due to safety reasons, tolerance induction in the form of SCIT has been abandoned in food allergic patients. Hence, an efficient and safe vaccine against IgE-mediated allergic diseases is needed.
The aim of the current project is to develop a novel type vaccine against food allergy. As a model for food allergy we have chosen shrimp allergy, since the majority of the patients with this allergy respond to only one allergen, tropomyosin. Shrimp tropomyosin is a heat-stable muscle protein. The amino acid sequence of invertebrate tropomyosins is highly conserved, with 95 % identity between shrimp and Storage mite (Tyrophagus putrescentiae). Tropomyosin was found to play an important role in the cross-reactivity seen between the different invertebrate species – suggesting tropomyosin to be an invertebrate pan-allergen.
Candidate vaccine - A schematic representation of the molecular structure of candidate vaccine against shrimp allergy. The shrimp allergen tropomyosin is linked to a ligand that inhibits the inflammatory response to the allergen.
The project partners in this project are the Norwegian Veterinary Institute, Norwegian and Italian Institutes of Public Health, Haukeland University Hospital, Oslo University Hospital and the Immunological Institute at the University of Oslo.
Status per January 2013:
We have generated and tested different vaccine candidates. One candidate has showed promising results in our tests with human blood and skin prick tests on shrimp allergic individuals, and in an animal model for shrimp allergy. Studies on this vaccine will be continued in our follow-up project ALLERVACC.
Myrset, H.R., et al., Structural and Immunological Characterization of Recombinant Pan b 1, a Major Allergen of Northern Shrimp, Pandalus borealis. International Archives of Allergy and Immunology, 2013. 160(3): p. 221-232.
Myrset HM and Dooper MMBW. IgE binding towards five peptides covering the entire sequence of Tropomyosin from the Northern Atlantic shrimp Pandalus Borealis. The 4th International Symposium om Molecular Allergology, October 29th-31th 2010, Munich, Germany.
HR Myrset, MMBW Dooper, K Thompson and E Egaas. Recombinant tropomyosin from Pandalus borealis, as model allergen for a novel vaccine against food allergy. 8th EAACI-GA2LEN-Immunology Winter School – Basic Immunology Research in Allergy and Clinical Immunology. Feb 11th- 14th 2010, Grainau, Germany (on invitation).