Preclinical Development of ARA-LAMP-Vax: A Promising Peanut Allergy Therapy
Abstract
The proposed research relates to the Fiscal Year 2014 Peer Reviewed Medical Research Program (PRMRP) Technology/Therapeutic Development Award announcement, particularly to the Food Allergy Topic Area. The prevalence of food allergy has doubled over the past decade and causes significant medical problems and high annual treatment and indirect costs, recently estimated to be $25B. Peanut allergy is the most common and severe form of food allergy. Avoiding peanut exposure is especially challenging, as many foods contain peanut, which may lead to unexpected allergic reactions. After peanut exposure, a constellation of allergic symptoms may develop that includes throat constriction, shortness of breath and wheezing, oral itching and tingling, and digestive problems. In more severe instances, peanut exposure can lead to trigger anaphylaxis, a rapid onset allergic reaction so severe it can lead to death. In the United States, around 100-200 deaths occur annually out of the 30,000 reported anaphylactic episodes. Peanut allergies are more common in children and disease management training, and programs have been implemented in schools and other public institutions at a high, but necessary, cost. There is no Food and Drug Administration (FDA)-approved treatment for peanut allergies, and a safe, effective peanut allergy treatment remains an area of high unmet medical need. To address the medical challenges of peanut allergy, Immunomic Therapeutics, Inc. (ITI) is working on a promising peanut allergy vaccine, ARA-LAMP-vax, with the potential to ameliorate the allergic condition of the 1.5 million peanut allergy sufferers in the United States. If successful in demonstrating safety and efficacy, this product could revolutionize peanut allergy treatment. Currently, those with a history of peanut allergy are unable to meet the medical standards for enlisting in military service. Treatment with ARA-LAMP-vax could potentially clear those receiving the vaccine to serve in the military. ARA-LAMP-vax is believed to work by retraining the allergic immune response to a non-allergic antigenic response and reduce IgE levels. By creating a long-lasting antigenic Th1 memory to the major peanut allergens, it is hypothesized that subsequent exposure will not result in an allergic reaction. Treatment is expected to involve four intradermal injections, once every 4 weeks. ARA-LAMP-vax has been designed provide a safe, fast and effective peanut allergy vaccine. The treatment is a DNA vaccine, which uses a minimally designed plasmid that upon injection produces the three major peanut allergens Ara h 1, Ara h 2, and Ara h 3, in targeted antigen presenting cells. The allergens are encoded as a fusion-protein with LAMP (Lysosomal Associated Membrane Protein-1) Technology, which accomplishes two goals of a next-generation peanut allergy vaccine: (1) Safety: By encoding the allergen as a LAMP fusion, the fusion protein traffics to the lysosome where it is subject to degradative enzymes prior to presentation to the immune system by MHC-II, which mediate how peanut proteins are presented to the immune system. The safety of the LAMP Technology has been tested in allergic human subjects, and no severe adverse events (AEs) were reported and very few AEs (mostly injection site soreness). (2) Immunogenicity: By ensuring high-fidelity MHC-II trafficking and stabilization of the complex fusion protein encoded in the vaccine, the LAMP Technology activates Th1 cells and after four vaccinations establishes therapeutic Th1 memory cells. ITI has tested ARA-LAMP-vax in a variety of experimental models designed to recapitulate human food allergies and found treatment to be safe and effective for both treating and preventing peanut allergies. These studies have been led by Dr. Teri Heiland and have involved sponsored research at the lab of Dr. Hugh Sampson, Mt. Sinai, New York. The product is ready for cGMP (current Good Manufacturing Practices) manu
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510610
Entities
People
- Teri Heiland
Organizations
- Immunomic Therapeutics (United States)
- United States Army