IgE Peptide Vaccine for Immunotherapy of Allergy

描述(由申请人提供)：该计划的最终目标是开发一种基于IgE多肽的免疫治疗性疫苗来治疗特应性患者。这种疗法的机制是产生抗LGE抗体反应，阻断其高亲和力受体与IgE的结合部位。这将防止IgE致敏肥大细胞和嗜碱性粒细胞，从而阻止导致过敏反应的级联反应的根本原因。这种疫苗有望下调IgE及其高亲和力受体的合成，并导致脱敏。与基于变应原的脱敏治疗或免疫治疗不同，基于IgE的疫苗将对所有不依赖变应原的IgE介导的过敏反应有效，预计只需注射三次即可有效。IgE疫苗的开发将使用两种已经发现的UBITh(R)肽免疫原，这两种免疫原具有通过新的UBITh(R)技术开发的具有免疫原性的有效T辅助位点，以及从epsilon重链的CH3区域获得的专有目标抗原位点，该区域影响IgE与其高亲和力受体的结合。多肽免疫原将使用UBIS新开发的免疫刺激复合体，结合多肽与疏水基团(脂肪作用)和矿物盐或油包水乳状液疫苗递送载体，以及肌肉内或无针头递送途径，制成有效和安全的疫苗。具体目的是通过以下方式确定基于多肽的IgE疫苗的可行性：1)通过测试和监测不良反应、过敏抗体、对IgE致敏的抑制和非LGE免疫毒性，显示在非人类灵长类动物(狒狒)中的安全性和有效性；2)确定多肽/免疫刺激复合体的最佳配方(脂类或非脂类、剂量、佐剂和给药载体)和注射途径(肌肉内或非针头)；3)证明通过生产大量临床级别的疫苗，疫苗生产过程的所有部分都可以扩大到符合GMP的生产水平；以及4)通过启动足够用于IND前会议的特征和文件进入临床试验路径。

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.