The Prospect of a Celiac Vaccine: Part 1

Photo courtesy Stock.Xchange / Leonardini

In recent weeks, the celiac world has been abuzz with news of promising clinical trials that hint at the potential of a vaccine for the disease. If you want to read any of the reports yourself, you can check out the National Foundation for Celiac Awareness’ news feed, Celiac.com, Science Daily, and International Business Times, just to name a few sources. Or, you can go straight to the horse’s mouth and read a PDF from the biotech research company, ImmusanT, or watch a YouTube video where the findings are explained by principle researcher Bob Anderson.

First, here’s an overview of who’s behind the vaccine: Bob Anderson Ph.D. is a faculty member and researcher at the Walter and Eliza Hall Institute of Medical Research in Australia, where he specializes in autoimmune conditions, including celiac disease. He also sits on the Medical/Scientific Advisory Board of the NFCA, and is the chief medical officer and chief scientific officer of ImmusanT, the Cambridge, MA-based biotech startup behind the vaccine.

Understanding Celiac Genetics and the Vaccine

To understand just how the vaccine works, I first want to take a step back and do a quick lesson in celiac genetics for the layperson (at least insofar as is relevant to the vaccine at hand…). The vaccine, known as Nexvax2, specifically targets the immune response of those celiac patients who carry the HLA-DQ2 gene.

Two genes – HLA-DQ2 and HLA-DQ8 – have been implicated in celiac disease. DQ2 is by far the more prevalent of the two. Actually, a significant minority of the population of western European descent (estimates hover in the 35% range) carries the DQ2 gene, even though they don’t have celiac disease. However, of patients with diagnosed celiac disease, a sizable majority (in the vicinity of 80%) carries the DQ2 gene.

As a result, the DQ2 gene is often considered to be (somewhat) necessary, but not sufficient, to diagnose someone with celiac. In other words, if you have celiac disease, there’s also a pretty good chance (though not 100%) that you carry the DQ2 gene.

From the standpoint of developing a vaccine of this type, it makes the most sense to target this population of celiacs, since you’re essentially capturing the largest segment of the population in one fell swoop.

The vaccine operates through the use of three proprietary peptides. Gluten, as you know, is a family of proteins. Proteins are made up of amino acids, which link together in short strands known as peptides, which further link together in longer strands known as polypeptides, which link together and fold even more to form complex proteins. But researchers have increasingly realized that it’s not the whole gluten protein that makes a celiac sick. It’s only certain peptide segments within the larger protein. Nexvax2 isolates three suspected peptides, and puts them into a single vaccine.

It’s important to understand that Nexvax2 is a therapeutic vaccine. You don’t take it before you have a disease, with the idea of inoculating yourself against a disease. Instead, the vaccine is used as a form of treatment after you’ve been diagnosed with an active condition. In this case, you need an active diagnosis of celiac disease, and be a carrier of the HLA-DQ2 gene. The vaccine then works similar to allergy therapy, where the patient is repeatedly exposed to controlled doses of the offending substance (in this case, gluten), with the idea of inducing tolerance. Said another way, scientists are experimenting with exposing diagnosed celiac patients to controlled amounts of the offending gluten peptides, so that your body “learns” the gluten and you no longer get sick from it. If the vaccine works as researchers hope it will, in theory you’d be able to eat gluten again.

It’s an approach that has showed promise with other conditions, such as asthma, and researchers are exploring the approach with relation to other autoimmune conditions as well.

Clinical Trial Methods and Results

The vaccine recently completed its Phase I clinical trial, during which it was tested for its safety and tolerability with a small number of human patients. 34 people – all positively diagnosed with celiac disease, positive for the HLA-DQ2 gene, and on a long-term gluten-free diet – were broken into five groups: placebo, plus four groups which each received different dose levels of the Nexvax2 vaccine weekly for three weeks.

Some patients experienced nausea and vomiting. Others, particularly among the groups that received higher doses of the vaccine, experienced gastrointestinal symptoms consistent with their celiac disease. One person’s symptoms were bad enough that they withdrew from the study. In follow up tests, patients showed T-cell (immune) responses to the vaccine.

Believe it or not, this was good news. For one, a phase I clinical trial, in addition to testing for safety and tolerability, helps researchers to hone in on appropriate dose levels. Just as importantly, the fact that celiac patients had celiac reactions to the vaccine confirmed for researchers that they had in fact isolated the appropriate gluten peptides.

Of course, this still leaves open the very big question of whether or not the vaccine will work as intended. That’s for phase II of clinical trials, which tests efficacy, and which researchers hope to begin within the next year.

Coming up in Part 2…

The vaccine has generated enormous amount of excitement within the gluten-free / celiac community. It’s also generated a fair bit of skepticism. And as might have been expected, rumors and misinformation have begun to circulate the blogosphere, and people are left with a number of lingering questions, such as What’s next? Where do we go from here? Would you get the vaccine, or stay gluten-free, or both? And what are the implications of these clinical trials?

We’ll tackle all that, and more, in Part 2, coming soon!

– Pete