Development of Nanoplasmid LAMP-based Peanut Allergy Immunotherapy. An estimated million Americans are allergic to peanut, which is the most common trigger of anaphylaxis resulting in over 30,000 incidents and between 100 - 200 deaths in the US each year. There are no FDA approved treatments for peanut allergy. In response to NIAID's commitment to address the health challenge posed by peanut allergies, Immunomic Therapeutics, Inc. ("ITI") proposes novel and innovative SBIR Phase I research to develop ARA-LAMP-vax by encoding the three major peanut allergens as a single lysosomal associated membrane protein ("LAMP") chimera to desensitize peanut allergic patients through a Th1-based mechanism, delivered using a recently developed Nanoplasmid with greatly enhanced gene expression and immunogenicity. ARA-LAMP-vax is a safe, short treatment course with long-lasting anaphylactic protection. ITI has successfully designed, tested and validated multiple antigen-LAMP-vax DNA formulations, with a therapeutic focus on treating IgE-mediated allergic diseases. Recently, ITI completed a Phase I clinical study of JRC-LAMP-vax, a plasmid-based immunotherapy for Japanese red cedar. When administered intramuscularly (IM) as naked DNA in saline four times, biweekly, no severe adverse events were reported and skin test conversion from Japanese red cedar positive to negative was observed and maintained in 14 out of 16 patients out through day 400. It is hypothesized that the observed desensitization is due to re-balancing of the allergic Th2 / immunoglobulin (Ig) E response by inducing a Th1 central memory response and high titers of allergen-specific IgG. The use of LAMP-vax in treating serious IgE-mediated diseases establishes a new level of safety by eliminating the risky exposure to free allergen as required in traditional immunotherapy. This Phase I research draws on ITI's experience in commercializing LAMP-based allergy vaccines, the innovations in plasmid design executed by ITI's long-time collaborators at Nature Technologies that led to the breakthrough in minimal plasmid design realized in the Nanoplasmid expression vector, and previous work that showed that a DNA-based multivalent peanut vaccine could provide therapeutic and prophylactic benefits in peanut allergic mice. Completion of the Aims herein will provide a clear rationale for commercializing the Nanoplasmid-based peanut allergy vaccine ARA-LAMP-vax. Phase I Aims are to: (1) design and synthesize peanut allergen-encoding Nanoplasmids; (2) Test ARA- LAMP-vax formulations in a prophylactic model of peanut allergy; and (3) Evaluate therapeutic efficacy in a mouse model of peanut anaphylaxis. During Phase II, ITI will prepare ARA-LAMP-vax, under current Good Manufacturing Practices (cGMP) and conduct biodistribution & toxicology studies in support of an IND filing. The goal of this project is to commercialize ARA-LAMP-vax. ITI strongly believes that this proposal supports NIAID's commitment to address the health challenge posed by food allergy and peanut-induced anaphylaxis, for which there is no FDA approved treatment.
Public Health Relevance Statement: Public Health Relevance: Public Health Relevance Peanuts allergies affect over a million Americans and are the most common cause of anaphylaxis, a potentially lethal allergic reaction. Peanut allergies disproportionately affect children and are rarely outgrown. A safe and effective treatment is urgently needed to desensitize individuals at risk of anaphylaxis due to peanut exposure.
Project Terms: Address; Affect; Allergen Immunotherapy; Allergens; Allergic; Allergic Disease; Allergic Reaction; Allergy to peanuts; American; Anaphylaxis; Antibiotic Resistance; Antibodies; Antigen Presentation; Antigens; Applications Grants; base; Biodistribution; Cells; Cessation of life; Child; Chimera organism; Chimeric Proteins; Clinical; Clinical Research; Clinical Trials; Computer Simulation; Control Groups; cytokine; Data; desensitization; design; Development; Disease; DNA; Dose; Drug Formulations; effective therapy; Ensure; Equilibrium; experience; Exposure to; expression vector; FDA approved; Food Hypersensitivity; Future; Gene Expression; Goals; Grant; Health; Human; Hypersensitivity; Hypersensitivity skin testing; IgE; Immune response; Immunization; immunogenic; immunogenicity; Immunoglobulin G; Immunotherapy; Inbred BALB C Mice; Inbred C3H Mice; Individual; innovation; Intramuscular Injections; Japanese Population; Mediating; Medical; Membrane Proteins; Memory; Modeling; mouse model; Mus; Nature; novel; Oral; Outpatients; Patients; Phase; Phase I Clinical Trials; Plasmids; pre-clinical; Preparation; prevent; Production; prophylactic; protein expression; Protocols documentation; public health relevance; Reporting; Research; Research Proposals; response; Risk; Safety; Saline; Severe Adverse Event; Small Business Innovation Research Grant; Symptoms; Technology; Testing; Therapeutic; Time; Toxicology; Translating; Transmembrane Domain; Treatment Efficacy; Vaccination; Vaccines; Validation; vector control; Western Blotting; Work
