Synthesis and Evaluation of Carbohydrate Vaccine Adjuvants

碳水化合物疫苗佐剂的合成与评价

• 批准号: 10538831
• 负责人: Hien M Nguyen
• 金额: $ 64.92万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-10 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10538831
• 关键词: Address; Adjuvant; Antibody Response; Antigen-Presenting Cells; Antigens; Applications Grants; Azides; B-Lymphocytes; Biodistribution; CD8-Positive T-Lymphocytes; Carbohydrates; Cell Maturation; Chemistry; Clinical; Clinical Trials; Communicable Diseases; Development; Ethers; Evaluation; Exhibits; Fluorides; Galactose; Generations; Glucose; Glycosides; Goals; High Pressure Liquid Chromatography; Human; Hydrogen Bonding; Hydroxyl Radical; Hypocotyl; Immune response; Immunity; Immunologics; Immunology; In Vitro; Iowa; Label; Link; Mediating; Medicinal Plants; Metabolic; Methods; Natural Products; Oligosaccharides; Plasma; Process; Production; QS21; Regulation; Respiratory Syncytial Virus Vaccines; Role; Safety; Saponins; Source; Soyasapogenol; Soyasaponin; Structure; Structure-Activity Relationship; T cell response; Therapeutic; Toxic effect; Triterpenes; Universities; Vaccination; Vaccine Adjuvant; Vaccines; Variant; aluminum sulfate; carbene; catalyst; chemical synthesis; clinical application; clinically relevant; combat; cost effective; cytokine; glycosylation; immunogenicity; improved; in vivo; mouse model; multidisciplinary; novel; novel vaccines; preclinical evaluation; screening; soy; success; tool; vaccinology

PROJECT SUMMARY The success of vaccination requires the generation of a strong immune response to the inoculated antigens in order to provide long-term protective immunity against many infectious diseases. To achieve this goal often requires the addition of vaccine adjuvants, substances that a substance that boosts the body’s immune response to the vaccine. However, there are only a few human vaccine adjuvants with an extensive safety record and minimal toxicity approved for clinical use. At presence, more studies are needed to identify novel adjuvants that not only significantly enhance the immune response for a particular vaccine, but also must be minimally toxic and maximally safe for clinical use. In efforts to discover novel vaccine adjuvants, an in vivo screening of forty-seven saponins from medicinal plants for their immunostimulatory and hemolytic activities has led to the discovery of new exciting vaccine adjuvants. Among forty- seven saponins evaluated, soyasaponins have emerged as the most potent adjuvants. These newly-discovered carbohydrates exhibited a significantly enhanced adjuvant activity with almost negligible toxicity when directly compared to QS-21 which has emerged as a vaccine adjuvant in numerous clinical trials. However, obtaining them from natural sources is a complicated process of extraction and purification that result in the production of minute. As a result, isolation of soyasaponins is economically unfeasible and unsustainable if sufficient quantities are required for immunological studies and clinical applications. Since FDA has strict regulations regarding to the purity and quality of adjuvants for use in human, a synthetic source must be developed for soyasaponins to be utilized as clinically relevant adjuvants. The objective of this proposal will address these challenges through the chemical synthesis for procuring sufficient quantities of soyasaponins in pure form. This effort will deliver well-defined soyasaponins without batch-to- batch variation and provide tools for studies of their roles as vaccine adjuvants and exploration of structure-adjuvant potency profiles for the discovery of non-natural soyasaponin improved adjuvants.

项目摘要 疫苗接种的成功需要对 接种抗原，以便为许多传染性提供长期保护的免疫力 疾病。为了实现这一目标，通常需要添加疫苗调节器，物质 一种可以增强人体对疫苗的免疫反应的物质。但是，只有一个 很少有人类疫苗佐剂具有广泛的安全记录和最少的毒性批准 临床用途。在场时，需要更多的研究来识别新的调节器，不仅 显着增强了特定疫苗的免疫反应，但也必须最小 有毒，最高安全的临床用途。为了发现新颖的疫苗调节器， 从医用植物的免疫刺激性和 溶血活动导致发现了新的令人兴奋的疫苗调节器。四十 - 评估了七个皂苷，大豆蛋白已成为最有效的调节蛋白。这些 新发现的碳水合物暴露了明显增强的调整活动，几乎 与QS-21直接进行比较，该毒性可以忽略 许多临床试验。但是，从天然来源获取它们是一个复杂的过程 提取和纯化导致分钟的产生。结果，隔离 如果需要足够的数量，大豆蛋白在经济上是不可行的和不可持续的 用于免疫研究和临床应用。由于FDA有严格的法规 在人类中使用的调节器的纯度和质量，必须开发合成源 大豆蛋白可用于临床相关的调节剂。该提议的目的将 通过化学合成来解决这些挑战 大豆蛋白以纯形式。这项努力将提供明确定义的大豆，而无需批次至 批处理变化并为研究其作为疫苗调节器和探索的作用提供工具 用于发现非天然大豆蛋白的结构 - 辅助效力概况 佐剂。