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Vesivaxâ® Peanut Allergy Immunotherapy

Investigators
Fujii, Gary
Institutions
Molecular Express, Inc.
Start date
2017
End date
2018
Objective
The current standard of care for peanut allergy is strict avoidance of peanuts. Due to the contaminationof various food items with peanut protein allergens, complete avoidance is difficult to achieve and reduces thequality of life in allergic individuals for fear of accidental ingestion. Upon accidental exposure, allergicindividuals must quickly self-administer or receive epinephrine injections and antihistamines to prevent thesymptoms associated with the onset of an allergic reaction. To treat peanut allergies, a more recent strategybeing tested is allergen-specific immunotherapy which focuses on preventing the development of allergicsymptoms by altering the pathologic immune response to non-pathogenic antigens and inducing clinicaldesensitization which is defined as an increase in the threshold of ingested allergen needed to cause allergicsymptoms. Clinical trials investigating long-term oral and sublingual delivery of escalating low doses of peanutproteins as a form of allergen-specific immunotherapy have been conducted and achieved some success atinducing clinical peanut desensitization in peanut-allergic individuals. The effectiveness of oral immunotherapyhas been demonstrated by the ability of peanut-allergic patients treated with active oral immunotherapy totolerate 5,000 mg of peanuts whereas placebo treated patients were only able to tolerate 280 mg of peanuts.However, the daily administration schedule and duration of treatment (>1 year) as well as the occurrence ofmild adverse effects such as itching and sneezing and, on rare occasions, severe respiratory reactions, aresome of the shortcomings of current peanut-specific mucosal immunotherapy. In addition, althoughdesensitization can be achieved by mucosal immunotherapy, long-term tolerance has yet to be demonstratedas half of the patients who are successfully desensitized regain sensitization after 4 weeks of allergenwithdrawal. In summary, the length of time required to achieve clinical desensitization, the potential ofexperiencing adverse effects associated with peanut-specific mucosal immunotherapy and the short durationof the desensitization of the immune response profile, while providing evidence that allergen-specificimmunotherapy can work, suggests that there is still room for improvement by the implementation of noveltherapies that reduce the time to desensitization and the possibility of adverse reactions. One strategy for improving current peanut immunotherapy protocols would be to design animmunotherapy formulation that rapidly induces long-lasting peanut-specific Th1 and T regulatory responseswhile minimizing adverse effects in a hypersensitive host. Sensitization to peanut allergens occurs by theinduction of peanut-specific T helper (Th) type 2 cells that secrete Interleukin (IL) -4, -5 and -13 to support Bcell production of peanut-specific IgE that binds mast cells (MC) and basophils. The major peanut allergenproteins are Ara h 1, 2, 3 and 6. It is estimated that 95% of peanut allergic individuals have IgE specific for Arah 1, 2 and 6 and 45% of peanut hypersensitive people have Ara h 3-specific IgE. Exposure to peanut inallergic hosts crosslinks surface IgE on mast cells and basophils inducing their degranulation and secretion ofinflammatory mediators that produce allergy symptoms. A recent publication described the ability of injectionimmunotherapy with peanut extract (PN) adjuvanted with the Toll-like Receptor (TLR)-9 agonist, CpG, toreduce allergic disease severity in mice. Since injection therapy is impractical due to the incidence of severeadverse reactions, mucosal delivery of immunotherapy formulations would be much more acceptable forclinical development. The Staats laboratory at Duke University has recently developed a mouse model ofnasal immunotherapy against peanut allergies and shown that a combination of PN adjuvanted with CpG inthis mucosal immunization model facilitated a reduction in the severity of peanut-induced anaphylaxis inhypersensitive mice in a manner that is superior to therapy with PN alone. In this SBIR Phase I application, we propose to demonstrate that VesiVax® liposome formulationscontaining immunostimulatory adjuvant molecules that have been shown to stimulate cellular immuneresponses can be used to re-direct the response of the immune system to an allergen into a non-allergicresponse profile. We will focus on peanut allergens to demonstrate the proof of concept that VesiVax®liposomes can facilitate the switching of the immune response to a non-allergenic response pattern. We willcollaborate with Professor Staats? laboratory to conduct these studies.
Funding Source
Nat'l. Inst. of Allergy and Infectious Diseases
Project source
View this project
Project number
1R43AI131788-01
Categories
Sanitation and Quality Standards
Commodities
Nuts, Seeds