IgE Peptide Vaccine for Immunotherapy of Allergy

用于过敏免疫治疗的 IgE 肽疫苗

• 批准号: 6896234
• 负责人: Chang Y. Wang
• 金额: $ 46.49万
• 依托单位: UNITED BIOMEDICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6896234
• 关键词: antiallergic agents; baboons; basophils; binding sites; biotechnology; clinical research; drug administration routes; drug delivery systems; drug design /synthesis /production; helper T lymphocyte; human tissue; hypersensitivity desensitization; immunoglobulin E; immunologic receptors; mast cell; nonhuman therapy evaluation; synthetic vaccines; vaccine development

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.

描述（由申请人提供）：该计划的最终目标是开发一种基于 IgE 肽的免疫治疗疫苗来治疗特应性个体。该疗法的机制是产生抗 IgE 抗体反应，阻断 IgE 上高亲和力受体的结合位点。这将阻止 IgE 使肥大细胞和嗜碱性粒细胞敏感，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。与基于过敏原的脱敏治疗或免疫疗法不同，基于 IgE 肽的疫苗将对所有 IgE 介导的过敏反应有效，与过敏原无关，并且预计只需注射 3 次即可有效。 IgE 疫苗将使用两种已发现的 UBITh(R) 肽免疫原进行开发，这些免疫原具有通过新型 UBITh(R) 技术开发的有效 T 辅助位点，具有免疫原性，以及取自 epsilon 重链 CH3 结构域的专有靶抗原位点，该位点影响 IgE 与其高亲和力受体的结合。肽免疫原将使用 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剂疫苗递送载体，以及肌内或无针递送途径，配制成有效且安全的疫苗。具体目标是通过以下方式确定基于肽的 IgE 疫苗的可行性： 1) 通过测试和监测不良反应、过敏性抗体、IgE 致敏抑制和非 IgE 免疫毒性，在非人类灵长类动物（狒狒）中显示安全性和有效性； 2) 确定肽/免疫刺激复合物的最佳配方（脂化或非脂化、剂量、佐剂和递送载体）和注射途径（肌内或无针）；3) 证明疫苗生产过程的所有部分都可以通过生产临床级批次的疫苗而扩大到符合 GMP 的生产水平； 4) 通过启动足以用于 IND 前会议的表征和文件，进入临床试验途径。