Despite significant advances in the development of potential treatments for food allergy, the approaches studied thus far have been limited by insufficient clinical responses and/or high rates of adverse reactions. While sublingual and epicutaneous immunotherapy (SLIT and EPIT) appear relatively safe, clinical responses have been disappointing, whereas with oral immunotherapy (OIT) more robust clinical responses come at the price of more frequent and severe adverse reactions. Further, it is clear that the benefits achieved with these treatments are usually not long lasting, reflecting a transient desensitization rather than any form of longer term tolerance, such that they will in all likelihood need to be used indefinitely to maintain protection. The ideal treatment will have a low risk of adverse reactions, a high rate of desensitization, a substantial level of protection, AND effects that will be truly sustained. Of the new modalities under current study, the most promising candidate to achieve these goals is ASP0892 (ARA-LAMP-vax). This novel compound is a single plasmid multivalent (Ara h1, h2, h3) lysosomal associated membrane (LAMP) DNA vaccine that is designed to radically shift the immune response to peanut allergens in sensitized patients. In brief, DNA encoding the peanut allergens Ara h1, h2 and h3 are inserted in tandem in a single plasmid containing the coding sequence for LAMP. Upon intradermal or intramuscular administration, uptake of the plasmid by antigen presenting cells results in the synthesis of an allergen-LAMP fusion protein. The LAMP component directs the fusion protein to cellular lysosomes where the allergen is processed and added to major histocompatability complex (MHC)-II antigens, which then stimulate a CD4+ helper T-cell response. Given that the peptide allergen is not released from the antigen presenting cells, it is anticipated that these immunoregulatory effects can be achieved with minimal or no risk of systemic allergic reactions to the vaccine. The central hypothesis of this protocol is that this novel immunotherapeutic approach, utilizing the LAMP associated plasmid DNA vaccine, will provide a safe, effective and long-lasting treatment for peanut allergy, with a long term goal of developing the next generation of immunotherapy for peanut and other food allergies.
|Sampson, Hugh A; Berin, M Cecilia; Plaut, Marshall et al. (2018) The Consortium for Food Allergy Research (CoFAR) The First Generation. J Allergy Clin Immunol :|