DEVELOPMENT OF SAPONIN DMLT ADJUVANT (SDA)

皂苷DMLT佐剂(SDA)的研制

• 批准号: 10935815
• 负责人: ELIZABETH NORTON
• 金额: $ 160.27万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 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/10935815
• 关键词: ADP ribosylation; Adjuvant; Antigens; Back; Biological Sciences; Campylobacter; Contractor; Cyclic GMP; Development; Dose; Enterotoxins; Evaluation; Food; Formulation; Goals; Human; Human poliovirus; Immunity; Mucosal Immunity; Mucous Membrane; Oral; Phase I Clinical Trials; Phase II Clinical Trials; Poliomyelitis; Poliovirus Vaccines; Preparation; Recording of previous events; Research; Route; Sampling; Saponins; Soapbush; Source; South American; Toxicology; Toxin; Trees; Vaccination; Vaccine Adjuvant; Vaccines; cross reacting material 197; enteric infection; enterotoxigenic Escherichia coli; gastrointestinal; immunogenicity; manufacture; mutant; novel; stability testing; success

Saponins derived from the South-American Tree Quillaja saponaria have a lengthy adjuvant history going back to 1925 and several saponin fractions are currently being utilized in commercial vaccines in humans. These are all injected vaccines and no mucosal saponin adjuvant currently exists. LT(R192G/L211A), or dmLT, is the product of more than 35 years of research on the use of bacterial ADP-ribosylating enterotoxins as adjuvants. dmLT has recently had success in Phase 1 and 2 clinical trials for ETEC and polio virus, though success for oral delivery seems to be dependent upon the immunogenicity of the antigen. Both adjuvants are pursued independently for various vaccines and delivery routes but have not been pursued together. In preliminary studies, we have observed synergistic adjuvant activity when dmLT and saponins are co-administered by oral and sublingual vaccination. In the current project, we propose to evaluate the novel combination saponin dmLT adjuvant (SDA) for oral or sublingual delivery utilizing expertise by both Tulane, Q-Vant Biosciences and PATH. We will optimize SDA in globally relevant vaccines including the U.S. Navy’s adjuvanted subunit ETEC and Campylobacter vaccine (ASEC) targeting bacterial enteric infections and inactivated polio vaccine. We will also explore novel formation preparations specific to gastrointestinal delivery and conduct IND-enabling studies such as GLP and cGMP manufacturing, toxicology, and stability testing. The ultimate goal of these studies is to define the SDA adjuvant platform and formulation that provides potent systemic immunity and/or sustained mucosal immunity.

源自南美树quillaja saponaria的s波蛋白可以追溯到1925年，并且目前在人类的商业疫苗中使用了几个皂苷的含量。这些都是注射疫苗，目前没有粘膜皂苷调整。 LT（R192G/L211A）或DMLT是超过35年的研究使用细菌ADP-核糖替型肠毒素作为佐剂的研究。 DMLT最近在第1阶段和2阶段的ETEC和脊髓灰质炎病毒方面取得了成功，尽管口服递送的成功似乎取决于抗原的免疫原性。两种佐剂都是为了各种疫苗和交付路线而独立追逐的，但尚未共同追求。在初步研究中，我们观察到当DMLT和皂苷通过口服和舌下疫苗接种时，可调节活性。在当前的项目中，我们建议评估新型组合Saponin DMLT调节器（SDA），用于使用Tulane，Q-Vant Biosciences and Path的专业知识进行口头或舌下交付。我们将在全球相关的疫苗中优化SDA，包括美国海军调整后的亚基ETEC和弯曲杆菌疫苗（ASEC）靶向细菌启动子感染和灭活脊髓灰质炎疫苗。我们还将探索针对胃肠道递送特有的新型形成制剂，并进行诸如GLP和CGMP制造，毒理学和稳定性测试之类的指定性研究。这些研究的最终目标是定义SDA调整平台和配方，以提供潜在的系统性免疫和/或持续的粘膜免疫。