Nexvax2 - 10 promising therapeutic vaccines

Vaccine: Nexvax2
Company: ImmusanT
Target: Celiac disease

A key challenge in developing any vaccine is picking the protein(s) best able to produce a strong immune response. Cambridge, MA-based start-up ImmusanT believes it knows those most likely to mitigate the damage done by celiac disease. Celiac disease comes about when people with a certain genetic makeup eat gluten, a protein naturally present in wheat, barley and rye. The mutation causes their bodies to perceive gluten as a danger; T cells that form to attack it soon begin destroying the intestinal lining.

Scientists behind ImmusanT's technology decided to investigate just what in gluten is provoking the aberrant and destructive immune response-and they did it much the same way that cancer vaccine developers seek potent antigens from tumor samples. The researchers broke the gluten protein down into about 2,700 distinct fragments, and tested the blood of 200 celiac disease patients against these. The immune response was then compared to that seen after the same people consumed wheat bread, rye muffins and boiled barley. The effort spotlighted three peptides as the main culprits: gliadin, hordein and secalin.

Nexvax2 is an experimental therapeutic vaccine that combines the three key gluten-derived peptides in saline solution. The goal of treatment, via weekly or monthly injections, is to desensitize celiac disease patients to the toxic effects of gluten. Phase I trial results reported in May showed that "symptoms and mobilization of gluten-specific T-cells observed after administration of Nexvax2 were similar to those triggered by acute oral gluten exposure in HLA-DQ2 patients on a gluten-free diet."

ImmusanT is collaborating with INOVA Diagnostics on a diagnostic test based on the peptides, to diagnose celiac disease and select patients with the right genetic makeup to benefit from Nexvax2. About 90% of all people diagnosed with celiac would qualify.

Similar approaches to vaccination might treat certain kinds of asthma, or even autoimmune diseases such as multiple sclerosis, type 1 diabetes and rheumatoid arthritis-but as ever, identifying the right antigens is the vital first step.