Comprehensive gluten T-cell epitope mapping in coeliac disease
Principal investigator: Dr Robert Anderson
Institution: Walter and Eliza Hall Institute, Victoria, Australia
Research classification: Underpinning research
Project completion: 2007
Grant awarded: £96K
This study was the first of its kind to determine the short fragments (epitopes) of gluten which are the most potent in triggering a reaction in people with coeliac disease. The results of this study and earlier research have been used to underpin the development of better diagnostic tests, non toxic gluten and a therapeutic vaccine which may offer an alternative treatment to the gluten-free diet.
Previous research at Oxford University showed that when people with coeliac disease who are normally on a gluten-free diet, deliberately eat gluten, their immune cells, called T-cells, reacting to gluten, emerge from the intestinal tissues and for a few days can be found in blood.
A library of epitopes encompassing all known gluten proteins that stimulate T-cells existed but those which are most damaging in people with coeliac disease were not known.
Volunteers with coeliac disease agreed to eat wheat, barley or rye and then provided blood samples. The T-cells found in the blood were specific for certain epitopes of gluten which were only present after eating specific grains.
This research project defined a “lead compound” for use as a desensitisation vaccine treatment for HLA DQ2-associated coeliac disease. This compound is the first to be designed according to the relevant T-cell activities measured using blood from people with coeliac disease after a gluten challenge.
Dr Bob Anderson has since established a commercial company for developing a therapeutic vaccine and diagnostics in coeliac disease.
Phase 1 clinical trials, to test the safety of the vaccine, were completed in 2010 in Australia where Dr Anderson was based at that time. Click here for more information on the Phase 1 clinical trials. The second phase trials will again be conducted in Australia but also in New Zealand and the US, where Dr Anderson is now based. Recruitment for the next phase of trials has begun, there are a limited number of participants, approximately 110 and they will be spread across several sites in the three countries, so five to six patients with coeliac disease per group. The purpose of these trials is to test the effects of increasing doses of the vaccine and how the body reacts to the vaccine.
The development of a vaccine is still a few years away but we will update the website as new developments unfold.
Tanner GJ, Howitt CA, Forrester RI et al. 2010 Dissecting the T-cell response to hordeins in coeliac disease can develop barley with reduced immunotoxicity. Aliment. Pharmacol. Ther. Nov;32(9) 1184-91.
Tye-din JA, Stewart JA, Dromey JA et al. 2010 Comprehensive, quantitative mapping of T cell epitopes in gluten in celiac disease. Sci. Transl. Med. Jul 21; 2(41): 41ra51.
Henderson, KN., Tye-Din JA., Reid, HH. et al. 2007 A structural and immunological basis for the role of HLA-DQ8 in celiac disease. Immunity Jul; 27 (1) 23-34.