Celiac Vaccine in Clinical Trials at Columbia

The only proven therapy for celiac disease—an autoimmune disorder that affects up to 3 million Americans—is to avoid dietary gluten. But this strategy is not always practical. Recent data from Columbia researchers suggest that as many as one-third of "gluten-free" restaurant meals contain trace amounts of the protein, which comes from wheat, rye, and barley. That is disconcerting for those with celiac disease, because even a tiny amount of gluten can launch an immune-system attack on the intestinal lining that can cause severe abdominal pain, diarrhea, and vomiting. 

In a few years, people with celiac may have a vaccine to protect themselves against accidental exposure to gluten. One of the first candidates, called Nexvax2, has just begun a phase 2 clinical trial that will test the vaccine’s effectiveness. Eligible patients will soon be able to enroll at Columbia’s Celiac Disease Center. 

The CUIMC Newsroom spoke with Peter Green, MD, director of Columbia’s Celiac Disease Center, about the vaccine trial and the need for therapies for those with celiac disease.

Why are researchers testing therapies for celiac disease? 

To prevent intestinal damage, individuals with celiac disease must completely avoid gluten. But this can be very difficult, and despite people’s best efforts many are inadvertently consuming gluten. Apart from the immediate effects of gluten on the GI system, the inflammation caused by the immune system’s reaction to gluten can prevent nutrients from being absorbed properly, which may lead to serious health problems such as osteoporosis, anemia, and infertility. 

So, there’s been great interest in developing therapies—including vaccines—for people with celiac disease. 

There are several drugs in the pipeline, and Columbia is participating in many of these studies. In addition to the vaccine trial, we are involved in studies to develop enzymes that may help individuals with celiac disease digest gluten and a drug that may prevent gluten from getting into the bowel wall. 

There are many other steps in the immune process that may offer potential therapeutic targets, though this vaccine is at the most advanced stage of development.

How does the vaccine work? Is it different from other vaccines, like the flu shot?

Most vaccines protect us from infectious agents, like viruses and bacteria. This celiac vaccine is a different type of immunotherapy, analogous to allergy shots, which increase an individual’s tolerance to a particular substance that triggers a big reaction. Celiac disease isn’t an allergy, but people with this condition develop a heightened immune reaction when they ingest gluten, similar to how people with an allergy to ragweed react when exposed to the plant.

The celiac vaccine is designed to reprogram the immune system so that it doesn’t go on the attack after small amounts of gluten are ingested. The vaccine does not prevent celiac disease from developing; it’s only useful for people who’ve already been diagnosed.

What will be tested in this new clinical trial?

Previous (phase 1) studies looked primarily at safety and have shown that the vaccine is well-tolerated, with no side effects. These studies have also identified a dose that may protect people from small amounts of gluten.

This phase 2 clinical trial, which is expected to enroll about 150 individuals with celiac disease in the U.S., Australia, and New Zealand, will help us determine if therapeutic vaccines are an appropriate way to protect individuals with celiac disease from the damage caused by ingesting gluten.

Because the trial tests the vaccine’s effectiveness over a limited period, additional studies will be needed to determine the dosing frequency to achieve a robust protective response.

Could anyone with celiac disease benefit from the vaccine? 

This particular vaccine is designed for those with a gene called HLA-DQ2.5, one of the two genes that increase the risk of celiac disease. Individuals with the other celiac gene, HLA-DQ8, will not respond to this vaccine. By far, the majority of those with celiac disease—around 90 percent—have HLA-DQ2.5.

The vaccine will not be administered to people who have HLA-DQ2.5 but have not developed any celiac symptoms. Fewer than 1 in 50 people with the gene go on to develop celiac disease, so the risk for these people–often family members of celiac patients–is not great enough to warrant giving them the vaccine. 

Would the vaccine allow someone with celiac disease to consume as much gluten as they wanted? 

As with all of potential therapies for celiac disease, the vaccine is designed to protect those who consume a small amount of gluten due to food contamination. If that works, then studies can be performed to assess whether the vaccine protects against exposure to larger amounts of gluten that may be found in non-gluten-free foods.