IgE Peptide Vaccine for Immunotherapy of Allergy

描述（由申请人提供）：本项目的最终目标是开发一种基于IgE肽的免疫抑制疫苗，用于治疗特应性个体。该疗法的机制是产生抗IgE抗体应答，其阻断IgE上的高亲和力受体的结合位点。这将防止IgE致敏肥大细胞和嗜碱性粒细胞，从而阻断导致过敏反应的级联反应的根本原因。预期这种疫苗下调IgE及其高亲和力受体的合成，并导致脱敏。与基于过敏原的脱敏治疗或免疫治疗不同，基于IgE肽的疫苗将对所有IgE介导的过敏反应有效，而不依赖于过敏原，并且预计在少至三次注射后有效。IgE疫苗将使用两种已经发现的UBITh（R）肽免疫原来开发，这两种免疫原具有通过新型UBITh（R）技术开发的用于免疫原性的有效T辅助位点，以及从IgE重链的CH 3结构域获得的专有靶抗原位点，其影响IgE与其高亲和力受体的结合。将肽免疫原配制成有效且安全的疫苗，使用UBI新开发的免疫刺激复合物结合肽与疏水基团的缀合（脂化）和矿物盐或油包水乳液疫苗递送载体，以及肌内或无针递送途径。1）通过测试和监测不良反应、过敏性抗体、IgE致敏的抑制和非IgE免疫毒性，在非人灵长类动物（狒狒）中显示安全性和有效性; 2）鉴定肽/免疫刺激复合物的最佳制剂（脂化或非脂化、剂量、佐剂和递送媒介物）和注射途径（肌肉注射或无针注射）;3）证明疫苗生产工艺的所有部分都可以通过生产临床级批次的疫苗来扩大规模，达到符合GMP的生产水平;和4）通过启动足以用于IND前会议的表征和文件来进入临床试验途径。

DESCRIPTION (provided by applicant): 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.