Anti-hIgE gene therapy of peanut-induced anaphylaxis in a humanized murine model of peanut allergy.

Publication TypeJournal Article
Year of Publication2016
AuthorsPagovich OE, Wang B, Chiuchiolo MJ, Kaminsky SM, Sondhi D, Jose CL, Price CC, Brooks SF, Mezey JG, Crystal RG
JournalJ Allergy Clin Immunol
Date Published2016 Dec
KeywordsAllergens, Anaphylaxis, Animals, Arachis, Cytokines, Disease Models, Animal, Female, Genetic Therapy, Histamine Release, Humans, Immunoglobulin E, Male, Mice, Mice, Inbred NOD, Peanut Hypersensitivity, Plant Extracts, Th2 Cells

BACKGROUND: Peanuts are the most common food to provoke fatal or near-fatal anaphylactic reactions. Treatment with an anti-hIgE mAb is efficacious but requires frequent parenteral administration.

OBJECTIVE: Based on the knowledge that peanut allergy is mediated by peanut-specific IgE, we hypothesized that a single administration of an adeno-associated virus (AAV) gene transfer vector encoding for anti-hIgE would protect against repeated peanut exposure in the host with peanut allergy.

METHODS: We developed a novel humanized murine model of peanut allergy that recapitulates the human anaphylactic response to peanuts in NOD-scid IL2Rgamma(null) mice transferred with blood mononuclear cells from donors with peanut allergy and then sensitized with peanut extract. As therapy, we constructed an adeno-associated rh.10 serotype vector coding for a full-length, high-affinity, anti-hIgE antibody derived from the Fab fragment of the anti-hIgE mAb omalizumab (AAVrh.10anti-hIgE). In the reconstituted mice peanut-specific IgE was induced by peanut sensitization and hypersensitivity, and reactions were provoked by feeding peanuts to mice with symptoms similar to those of human subjects with peanut allergy.

RESULTS: A single administration of AAVrh.10anti-hIgE vector expressed persistent levels of anti-hIgE. The anti-hIgE vector, administered either before sensitization or after peanut sensitization and manifestation of the peanut-induced phenotype, blocked IgE-mediated alterations in peanut-induced histamine release, anaphylaxis scores, locomotor activity, and free IgE levels and protected animals from death caused by anaphylaxis.

CONCLUSION: If this degree of persistent efficacy translates to human subjects, AAVrh.10anti-hIgE could be an effective 1-time preventative therapy for peanut allergy and possibly other severe, IgE-mediated allergies.

Alternate JournalJ. Allergy Clin. Immunol.
PubMed ID27372563