Cooperative program U01 AG060965 Supplement: "Preparation of IND for Dual Aβ/Tau AD Vaccine for submission to FDA"

合作计划 U01 AG060965 补充：“双 Aβ/Tau AD 疫苗 IND 的准备以提交给 FDA”

基本信息

批准号：
10505652
负责人：
Michael G Agadjanyan
金额：
$ 29.77万
依托单位：
INSTITUTE FOR MOLECULAR MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-02-01 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10505652
关键词：
Adjuvant Administrative Supplement Alzheimer disease prevention Alzheimer&apos s disease model Amyloid beta-Protein Antibodies B-Lymphocytes Biological Biological Markers Cells Certification Chemicals Chemistry Clinical Data Clinical Protocols Clinical Research Cyclic GMP Data Disease Disease Progression Genetic Polymorphism Goals Guidelines Human Immunotherapeutic agent Immunotherapy Inbreeding Infection Inflammation Injections Instruction Investigation Investigational Drugs Investigational New Drug Application Longevity Memory Monkeys Monoclonal Antibodies Mus Nerve Degeneration Neurologist Oryctolagus cuniculus Pamphlets Pathologic Pathologic Processes Persons Pharmaceutical Preparations Pharmacology and Toxicology Phase I Clinical Trials Placebos Preparation Preventive Preventive measure Preventive treatment Preventive vaccine Product Labeling Production Psychiatrist Publishing Reporting Research Personnel Risk Safety Scientist Specialist Therapeutic Toxic effect Toxicology Vaccines adaptive immunity autoreactive T cell base cGMP production disorder risk immunogenic immunogenicity medication safety mouse model nonhuman primate pathogen phase I trial pre-clinical preclinical study programs response tau Proteins vaccine evaluation vaccine platform vaccine trial

项目摘要

Project Summary Immunotherapy is still considered a very promising therapeutic strategy for AD prevention when certain conditions are met. Data from various immunotherapeutic studies support our long- standing tenet that immunogenic AD vaccines could at least delay disease progression when they target both Aβ and Tau pathological molecules at an early stage of the disease before AD manifestation. It is impractical to use very expensive mAbs as a preventive treatment of healthy subjects due to the need for frequent (monthly) administration of high concentrations (700-800mg per IV injection) of this immunotherapeutic. In contrast, almost all vaccines are effective in preventive settings. Accordingly, we seek an administrative supplement to U01 AG060965 that will support the preparation and submission of regulatory documents to the FDA to support the initiation of Phase 1 clinical trial of the dual preventive vaccine. Our proprietary vaccine platform can stimulate adaptive immunity, providing broad coverage of human MHC polymorphisms and activating both naive Th cells and pre-existing memory Th cells generated in response to conventional vaccines and/or infections with various pathogens during one's lifespan without the activation of harmful autoreactive T cells. These "non-self" Th cells should activate B cells and induce the production of therapeutically potent antibodies specific to pathological Aβ and Tau in humans similar to that we observed in inbred WT and Tg mice as well as outbred rabbits and monkeys. If safe and immunogenic in Phase 1 trials, the combined AV-1959R/A, and AV-1980R/A vaccines could be used as a preventive measure in healthy people at risk of MCI (based on biomarkers) to delay AD.

项目概要免疫疗法仍然被认为是一种非常有前途的 AD 预防治疗策略满足某些条件。来自各种免疫治疗研究的数据支持我们的长期观点。长期坚持的原则是，免疫原性 AD 疫苗至少可以延缓疾病进展在 AD 之前疾病的早期阶段针对 Aβ 和 Tau 病理分子使用非常昂贵的单克隆抗体作为健康的预防性治疗是不切实际的。由于需要频繁（每月）施用高浓度（700-800mg）的受试者相比之下，几乎所有疫苗都有效。因此，我们寻求对 U01 AG060965 的行政补充：将支持监管文件的准备并向 FDA 提交，以支持启动双重预防疫苗的一期临床试验。可以刺激适应性免疫，广泛覆盖人类 MHC 多态性，激活初始 Th 细胞和响应于响应而产生的预先存在的记忆 Th 细胞常规疫苗和/或在一生中感染各种病原体而没有激活有害的自身反应性 T 细胞，这些“非自身”Th 细胞应该激活 B 细胞和诱导产生针对病理性 Aβ 和 Tau 的治疗有效抗体人类与我们在近交系 WT 和 Tg 小鼠以及远交系兔子中观察到的情况相似如果在 1 期试验中安全且具有免疫原性，则组合 AV-1959R/A 和 AV-1980R/A 疫苗可用作有 MCI 风险的健康人群的预防措施（基于生物标志物）来延缓 AD。