The eventual goal of this program is to develop an IgE peptide-based immunotherapeutic vaccine to treat atopic individuals. The mechanism for this therapy is to generate an anti-lgE antibody response that blocks the binding site on IgE for its high affinity receptor. This will prevent IgE from sensitizing mast cells and basophils and thus block the root cause of the cascade that leads to allergic reaction. Such a vaccine is expected to down-regulate the synthesis of IgE and of its high affinity receptor, and to result in desensitization. Unlike allergen-based desensitization treatment or immunotherapy, the IgE-peptide based vaccine will be effective for all IgE-mediated allergic reactions independent of allergen, and is expected to be effective after as few as three injections. The IgE vaccine will be developed using two already discovered UBITh(R) peptide immunogens that have potent T helper sites for immunogenicity developed through the novel UBITh(R) technology, and a proprietary target antigenic site taken from the CH3 domain of the epsilon heavy chain that affects binding by IgE to its high affinity receptor. The peptide immunogens are to be formulated into effective and safe vaccines using UBIs newly developed immunostimulatory complexes in combinations with conjugation of the peptides to a hydrophobic group (lipidation) and mineral salt or water-in-oil emulsion vaccine delivery vehicles, and intramuscular or needle-less delivery routes.
The specific aims are to establish feasibility for the peptide-based IgE vaccine by: 1) Showing safety and efficacy in a non-human primate (baboons) by testing and monitoring for adverse reactions, anaphylactic antibodies, inhibition of IgE sensitization, and non-lgE immunotoxicity; 2) Identifying the most optimal formulation for the peptide/immunostimulatory complex (lipidated or non-lipidated, dosage, adjuvant and delivery vehicle) and route of injection (intramuscular or needle-less);3) Demonstrating that all parts of the vaccine production process can be scaled up to the level of GMP-compliant manufacturing by producing a clinical-grade lot of vaccine; and 4) Entering into the clinical trial pathway by initiating characterizations and documentation sufficient for a pre-IND meeting.
