10 Jan 2019
Clinical trials for a new coeliac disease vaccine are being fast tracked by the US Food and Drugs Administration (FDA) due to promising initial results.
Coeliac disease is caused by an autoimmune response to gluten and affects approximately 1 in 100 people worldwide. Those affected must eat a gluten-free diet, or experience uncomfortable digestive symptoms, mouth ulcers, fatigue and anaemia. If untreated, there is an increased risk of further complications, such as osteoporosis, neurological conditions, such as gluten ataxia, and even an increased risk of small bowel cancer. Researchers from innovative company ImmusanT have developed a first-of-its-kind vaccine against coeliac disease, which could offer a solution to patients.
Problems occur for coeliac disease patients when they are exposed to gluten - a protein found in wheat and other grains - and the immune system is triggered to attack the body. This results in inflammation, mainly in the intestines, and causes the subsequent acute symptoms related to the condition. Changes in the bowel can lead to the malabsorption of nutrients and long-term damage. Coeliac disease has no clinical treatment, aside from a restricted, gluten-free diet.
‘Currently, there are no disease-modifying therapies for this condition, and the only solution for patients is strict adherence to a lifelong, gluten-free diet,’ said Leslie Williams, CEO for ImmusanT. While this gluten-free diet prevents intestinal inflammation, even a small amount of gluten can trigger a reaction, making management difficult and negatively impacting a patient’s quality of life.
Coeliac disease is an autoimmune disorder. Generally, an immune response occurs when immune cells, known as T cells, are triggered by disease antigens, causing them to release chemicals known as cytokines. These chemicals cause an inflammatory response which leads to symptoms of infection. Antibodies relating to the immune-system trigger are also produced. Usually, an immune response occurs when the body is infected by a foreign body, such as a bacterial infection, but in the case of coeliac disease, the presence of gluten, or gluten-derived peptides, causes the immune response.
Dr Robert Anderson of ImmusanT speaking about the Nexvax2 coeliac vaccine at the Coeliac Disease National Conference in 2018. Video: Celiac Disease Foundation
Due to its severity, coeliac disease has been widely studied and genes have been identified that relate to the condition. Over 90% of coeliac disease patients carry immune recognition genes known as HLA-DQ2.5. These genes are human leukocyte antigen (HLA) genes, which usually relate to specific diseases. ImmusanT, a leader in the development of therapies for autoimmune disorders, has developed a vaccine that targets patients carrying the HLA-DQ2.5 genes. This novel therapeutic vaccine, known as Nexvax2, works by reprogramming specific T cells that are responsible for triggering an inflammatory response when gluten is consumed.
Nexvax2 consists of a combination of three short gluten-derived peptides and is administered via a subcutaneous injection, like that of other commercially available vaccines. Nexvax2 has already completed multiple Phase 1b clinical trials, providing positive results in the areas of safety, tolerability, proof of mechanism and effectiveness.‘Using a novel panel of coeliac disease-associated immunological markers, identified in early clinical studies, we can follow both acute symptoms and the underlying inflammatory response following gluten exposure,’ said Ken Truitt, Chief Medical Officer for ImmusanT. ‘We have high hopes that immunomodulation with Nexvax2 can help the majority of coeliac patients live without fear of inadvertent gluten exposure and associated health problems.’