Therapeutic Vaccine For Walnut and Pecan Allergies

IgE-mediated food allergies have become a major public health concern, now estimated to affect 6-8% of childrenunder 4 years old and 4% of adults in the US. Approximately 200,000 emergency hospital visits are caused fromallergic reactions to foods annually, with at least 150 fatalities resulting from anaphylaxis. The overall economiccost of food allergies in the US is estimated at $25 billion. There are currently no FDA-approved treatments forfood allergies and as such the only options available to allergic individuals are strict dietary avoidance of theallergen and emergency treatment with epinephrine if a reaction occurs. Allergic reactions to tree nuts, includingwalnuts and pecans, often result in life-threatening anaphylactic reactions and, along with peanut, are the primaryfoods known to trigger fatal reactions. Accidental exposures to nut allergens are common, since nuts can behidden in foods or contaminate foods served in restaurants and cafeterias. Tree nut allergies are rarely outgrownand have increased in prevalence over the past decade and are now estimated to affect greater than 1% of theUS population. While some treatments, including oral and epicutaneous immunotherapies, are beinginvestigated for peanut allergies, there are no rigorous studies being conducted in subjects with tree nut allergies.Unfortunately, the benefits of these desensitization therapies are typically mild to moderate and in most casesare short-lived. Therapeutic vaccination is a new and exciting potential treatment option for allergies that requirea considerably abbreviated treatment schedule and may have more profound and longer-lasting effects. Mosttherapeutic vaccination approaches being tested seek to reduce the symptoms caused by Th2-driven IgE byshifting the anti-allergen immune responses toward a Th1 phenotype characterized by IgG antibodies. Geneticvaccination approaches are among the most promising of the therapeutic vaccination approaches beinginvestigated. Three main types of seed storage proteins (legumins, vicilins, and 2S albumins) bind IgE and causeallergic symptoms to walnuts and pecans. Targeting these nut proteins represents a sound strategy fortherapeutic vaccination. Under this phase I SBIR, we intend to test an adjuvanted multi-valent walnut/pecantherapeutic DNA vaccine co-expressing a Th1 polarizing genetic adjuvant in a pre-clinical mouse model of walnutand pecan allergies. If our vaccine can be used to treat walnut and pecan allergic mice to successfully preventanaphylaxis upon oral challenge, we will continue development under phase II by performing toxicology studiesand beginning GMP manufacturing of the vaccine to support an IND application.2