There has been quite a buzz recently over a new vaccine for those that suffer from Celiac Disease. Will it successfully treat the autoimmune disorder and eliminate the need to adhere to a gluten free diet?
July 22nd, 2010 the Walter and Eliza Hall Institute announced that a group of Doctors and Scientists had identified the three protein fragments toxic to people with Celiac Disease. The research group headed by Dr. Bob Anderson head of the Walter and Eliza Hall Institute’s Coeliac Disease Research Laboratory, published their findings in the international journal Science Translational Medicine.
The Doctors and Scientists studied more than 200 Celiac Disease patients. The patients ate bread, rye muffins or boiled barley. Six days later, blood samples were taken to measure the strength of the patients’ immune responses to 2700 different gluten fragments (peptides). The responses identified 90 fragments as causing some level of immune reaction, but 3 gluten fragments were revealed as being particularly toxic, causing the majority of immune response in those with Celiac Disease.
Dr. Anderson, who is also the CEO of Nexpep Pty. Ltd., a Melbourne based biotech company, incorporated these findings of the 3 proprietary peptides to develop a ‘peptide-based’ immunotherapy. The goal; create a vaccine to desensitize people with Celiac Disease to the toxic effects of gluten by injecting patients with small amounts of the three toxic peptides. This is based upon the same principles as desensitization for allergies.
Testing a Vaccine:
The Phase I trial undertaken in Melbourne, Australia, evaluated the safety, tolerability and bioactivity (T-Cell Response) of the vaccine developed by Dr. Andersons’ Nexpep Pty. Ltd., known as Nexvac2. During Phase I trials weekly injections were administered over a three week period. 34 healthy celiac patients of the HLA-DQ2 genotype who were on a strict gluten-free diet took part in this trial. 19 subjects were given the vaccine while the others were given a placebo. Three different dosages; 30 micrograms, 60 micrograms and 90 micrograms were administered to the 19 subjects. Subjects experienced some nausea and gastrointestinal distress, but these symptoms were worse for patients receiving the highest doses. These patients had gastrointestinal symptoms similar to what they’d experience after eating gluten products and included vomiting. One subject receiving 90 micrograms withdrew from the study due to extreme gastrointestinal distress. Dr. Anderson and team believe this suggests the vaccine uses the correct peptides for eventually being able to tolerate gluten.
My Personal Thoughts:
As a Mother of a child with severe Celiac Disease, and a wife whose husband has silent/latent Celiac Disease, I question the current and future efficacy of this vaccine. Several questions come to mind when I read the details of this study. Dr. Anderson and his team found 2,700 gluten fragments (peptides) in the patients systems after ingesting wheat, barley and rye. Of those 2,700 they believed that 90 fragments were causing a reaction to gluten. The team then determined that the worst reactions were caused by 3 fragments, so that is where their focus lies, on only 3 of 2,700 potentially toxic peptides.
Another concern is that all grains contain gluten. Dr. Anderson and team have only studied the effects of wheat, barley, and rye in this trial. I have not found, in any of my research, their plans to incorporate other grains into their testing methodology. Dr. Anderson admits that many Celiacs on a strict gluten free diet (a diet restricting wheat, barley and rye) still show signs of damage to their small intestine 2-5 years after removing gluten from their diets. Could it be that healing has not occurred because Celiac patients have not eliminated all gluten containing grains from their diet?
While the news of this vaccine sounds promising Dr. Anderson and team will not know for many years whether these 3 “proprietary” peptides are truly the ones that cause damage to the small intestine. We must also keep in mind that to date this vaccine has only been given to 19 people, those who carry the HLA-DQ2 genotype. This genotype accounts for the majority of Celiac patients, approximately 80%, however, efficacy for patients who are HLA-DQ8, HLA-DR3 and those with Gluten Sensitivities has yet to be determined.
The Future of Nevax2 – Phase IIa Trials and Beyond:
Dr. Anderson’s Nexpep Pty. Ltd. was brought into the U.S. market, and is now ImmusanT. Leslie J. Williams, a former venture partner with Battelle Ventures is now President and CEO of the privately held startup, and Dr. Anderson holds the position of Chief Scientific and Medical Officer.
It is expected that ImmusanT will begin Phase 2a trials of the Nexvax2 vaccine within the year. The goal of Phase II is to demonstrate a dramatic reduction in the body’s rejection of dietary gluten. Anderson believes that upon repeated Nexvax2 administration, the number of gluten-specific T cells capable of triggering a pro-inflammatory response will subside, and regulatory suppressor T cells will increase in number to establish tolerance to dietary gluten.
Future plans for ImmusanT include collaborating with INOVA Diagnostics to improve and eventually replace the current testing substrates (including endoscopy) for Celiac Disease diagnosis. Work to discover peptides for other variants of Celiac Disease (HLA-DQ8, and HLA-DR3). Prevent Celiac Disease with Nevax2 in genetically susceptible patients, and use the vaccine for patients with IBS that respond to a gluten free diet.