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Synthesis and Evaluation of Carbohydrate Vaccine Adjuvants

碳水化合物疫苗佐剂的合成与评价

基本信息

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
项目类别：
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

项目摘要

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.

项目总结