DEVELOPMENT OF UM-1098: A NOVEL SYNTHETIC TH17 INDUCING ADJUVANT AND DELIVERY SYSTEM

UM-1098 的开发：一种新型合成 TH17 诱导佐剂和递送系统

基本信息

批准号：
10935819
负责人：
JAY EVANS
金额：
$ 241.99万
依托单位：
UNIVERSITY OF MONTANA
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-30 至 2028-09-29
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10935819
关键词：
Adjuvant Antigens Aspergillus fumigatus Bordetella pertussis Candida albicans Cells Chemistry Clinical Trials Contractor Contracts Development Drug Kinetics Excretory function Family suidae Formulation Human Humoral Immunities Immune response Immunity Investigation Ligands Mediating Metabolism Modeling Mus Mycobacterium tuberculosis Mycobacterium tuberculosis antigens National Institute of Allergy and Infectious Disease Production Property Pseudomonas aeruginosa Rodent Safety Staphylococcus aureus Streptococcus pneumoniae Structure-Activity Relationship System Toxicology Trehalose Vaccination Vaccine Adjuvant Vaccines absorption combat efficacy study immunogenicity improved manufacture mouse model nanoparticle delivery nonhuman primate novel novel vaccines pathogen pathogenic bacteria pathogenic fungus programs receptor research clinical testing thermostability

项目摘要

The development and clinical evaluation of safe and effective Th17 inducing adjuvants is urgently needed for the advancement of vaccines to combat the ongoing threat of bacterial and fungal pathogens including Mycobacterium tuberculosis (Mtb), Bordetella pertussis, Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumonia, Candida albicans, Aspergillus fumigatus and others. Vaccination against TB and other bacterial and fungal pathogens has been hampered by the lack of appropriate adjuvants for inducing Th17 immunity. Thus, the next generation of vaccine adjuvants capable of inducing broadly protective immune responses against emerging bacterial and fungal pathogens represents a critical unmet need. This Adjuvant Development Contract will advance one such adjuvant – UM-1098: a Th17 inducing synthetic Mincle ligand– towards human clinical trials. UM-1098 was identified through the NIAID Adjuvant Discovery Program via a comprehensive and iterative structure-activity relationship (SAR) investigations to identify a novel synthetic diaryl trehalose Mincle receptor ligand paired with a novel nanoparticle delivery system. This adjuvant and delivery system has a well-established safety and efficacy profile in mice, pigs and non-human primates (NHPs) across multiple highly relevant antigen/pathogen platforms including TB and Bordetella pertussis. The advantages of UM-1098 over previously developed Mincle adjuvants includes improved formulation physiochemical properties, thermostability, robust safety profile, and most importantly, superior antigen-specific Th17, Th1, and humoral immunity across rodents, pigs and NHPs. When co-administered with an antigen, UM-1098 adjuvant induces durable cell-mediated and humoral immunity with demonstrated protection against Mtb and Bordetella pertussis challenge.

The development and clinical evaluation of safe and effective Th17 induced adjuvants is urgently needed for the advancement of vaccines to combat the ongoing threat of bacteria and fungal pathogens including Mycobacterium tuberculosis (Mtb), Bordetella pertussis, Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumonia, Candida白色念珠菌，曲曲霉和其他人。缺乏适合诱导TH17免疫史的调节剂，阻碍了针对结核病和其他细菌和真菌病原体的疫苗接种。这是下一代疫苗调节器，能够诱导广泛保护的免疫复杂，以抗新兴细菌和真菌病原体，代表了至关重要的未满足需求。该辅助发展合同将推进一个这样的调节器-UM-1098：TH17诱导的合成大小配体 - 朝着人类的临床试验。通过NIAID调整发现程序通过全面且迭代的结构活性关系（SAR）研究来鉴定UM-1098，以鉴定新型的合成日记纪二摩尔三甲糖受体配体与新型的纳米颗粒递送系统配对。在多个高度相关的抗原/病原体平台（包括TB和Bordetella tuspussis）中，该调整和输送系统在小鼠，猪和非人类隐私（NHP）中具有完善的安全性和效率。 UM-1098比先前开发的Mincle佐剂的优点包括改进的配方生理化学特性，热稳定性，可靠的安全性，最重要的是，跨啮齿动物，猪和NHP的优质抗原特异性TH17，TH1和体液免疫学。当与抗原共同管理时，UM-1098可调节会诱导耐用的细胞介导的体液免疫学，并显示出对MTB和Bordetella budtussis挑战的保护。