mRNA Vaccine for Peanut Allergy

FY21 PRMRP Topic Area Addressed: Food Allergies

Overview: Food allergies affect 6%-10% of children and 10% of adults in the United States, impacting over 30 million citizens and their families. Food allergies are costing the U.S. healthcare system an estimated $25 billion annually. Importantly, food allergies exclude potential military personnel from enlisting, and have been shown to decrease the quality of life for patients and their families. Peanut allergy, in particular, has an estimated prevalence of above 1% of the population, a substantial increase over the past 15 years. Allergic reactions to peanut are often severe and account for the majority of fatal reactions. There is currently only one U.S. Food and Drug Administration (FDA)-approved therapy, Palforzia, for peanut allergy, based on oral immunotherapy (OIT) protocols. OIT involves daily intake of peanut proteins and can lead to desensitization for many patients. However, OIT has several limitations, including allergic side effects, required daily dosing, and a return to allergic status once OIT is discontinued.

Critical Research Problem: There is an urgent need for novel treatments for food allergies, particularly therapies that are safe, administered infrequently, and long-lasting. Currently, patients are instructed to avoid the allergen and be ready to manage allergic reactions with Epinepherine and anti-histamines, even for the small percentage of peanut-allergic subjects on OIT. Avoidance is very difficult and can cause great anxiety for patients and their families. Effective therapies would greatly increase the safety for patients with food allergies and decrease their anxiety. Novel therapies may also allow food allergic individuals to join the military.

Innovation: This project is highly innovative in several ways. Most importantly, we aim to develop and test the first mRNA vaccine for food allergy using established mouse models of peanut allergy. mRNA vaccines have gained traction during the COVID-19 pandemic as two companies, Moderna and Pfizer, have brought forth safe and highly effective vaccines aimed at the viral Spike protein, to stop the spread and disease severity brought on by SARS-CoV-2 infection. Furthermore, the delivery of our peanut mRNA vaccine via Gene Gun is a novel approach. The Gene Gun works by delivering the vaccine to the outer layer of the skin, where it will be presented to the immune system. The Gene Gun uses helium to propel the vaccine and has been found to be painless when applied to humans. We expect three vaccine doses to produce enough therapeutic antibody to prevent subsequent reactions to peanut. If successful, this will provide a significant advantage over traditional immunotherapy approaches (e.g., OIT) that require daily dosing. Furthermore, we anticipate the therapeutic antibody response to be long-lasting, which provides another advantage to the transient desensitization induced by OIT.

Ultimate Applicability and Impact of Research: If successful, we would use the animal data to communicate with the FDA to potentially bring this mRNA vaccine into human studies. Furthermore, this mRNA platform could be easily adaptable to any food allergen with a known DNA sequence (e.g., walnut, cashew, shellfish, egg, milk), insect stings, and environmental allergens (e.g., cats, dogs, pollens, molds). If successful, our approach to use mRNA vaccines to treat food allergy could pave the way for next-generation allergy therapies.