Development of ProtollinTM Plague Vaccine

ProtollinTM鼠疫疫苗的研制

基本信息

批准号：
6845743
负责人：
GEORGE H LOWELL
金额：
$ 799.24万
依托单位：
ID BIOMEDICAL CORPORATION OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-09-30 至 2007-08-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The aim of this work is to develop a nasal sub-unit Plague vaccine using the recombinant Plague antigen F1V formulated with ProteosomeTM-based ProtollinTM adjuvant to provide protection against the bioterror threat posed by aerosol-delivered Y. pestis. The primary aim of this application is to develop this product through early stage clinical trials. The long-term objective is to advance this recombinant sub-unit nasal Plague vaccine to licensure. The Protollin adjuvant component of the vaccine in development will be comprised of a one to one ratio of outer membrane proteins from N. meningitidis and LPS extracted from E. coll. The subunit antigen is recombinant FIV produced in a proprietary E. coil based expression system. At project commencement, a sufficient quantity of Protollin-F1V vaccine will be produced using established production methods. Coincident with preliminary mouse studies, a process development effort will focus on scale-up and validation of the production process, including characterization and QC testing, to support an IND. Initial studies will identify the efficacious dose range for both Protollin and F1V in an established mouse model of immunogenicity and efficacy. A toxicology study will be conducted using standard protocols to support an IND. A distribution using immunohistochemistry techniques also will be conducted to further assess the safety of this nasal product. We intend to conduct Phase 1 and Phase 2 studies using Protollin-F1V vaccine manufactured under cGMP guidelines. The Phase 1 study will examine a two dose regimen of escalating doses of vaccine to establish a safety profile for the product in man. The Phase 2 study will compare dose regimens of 2 or 3 doses at the optimal vaccine dose. Concurrent with the Phase 2 study, immunogenicity and efficacy studies will be conducted in a non-human primate model of aerosol Plague challenge to compare the nasal vaccine with an aluminum adjuvanted intramuscular F1V vaccine using Protollin-FIV doses selected from the Phase 1 clinical trial.

描述（由申请人提供）：这项工作的目的是开发一种鼻亚单位鼠疫疫苗，使用重组鼠疫抗原 F1V 与基于 ProteosomeTM 的 ProtollinTM 佐剂配制而成，以提供针对气溶胶传播的鼠疫耶尔森氏菌造成的生物恐怖威胁的保护。该申请的主要目的是通过早期临床试验开发该产品。长期目标是推动这种重组亚单位鼻鼠疫疫苗获得许可。正在开发的疫苗的 Protollin 佐剂成分将由一比一比例的脑膜炎奈瑟氏球菌外膜蛋白和从大肠杆菌中提取的脂多糖组成。亚单位抗原是在专有的基于大肠杆菌的表达系统中产生的重组 FIV。项目开始时，将使用既定的生产方法生产足够数量的 Protollin-F1V 疫苗。与初步小鼠研究相一致，工艺开发工作将侧重于生产工艺的放大和验证，包括表征和质量控制测试，以支持 IND。初步研究将确定 Protollin 和 F1V 在已建立的免疫原性和功效小鼠模型中的有效剂量范围。将使用标准方案进行毒理学研究以支持 IND。还将使用免疫组织化学技术进行分布，以进一步评估该鼻用产品的安全性。我们打算使用根据 cGMP 指南生产的 Protollin-F1V 疫苗进行第一阶段和第二阶段研究。第一阶段研究将检查疫苗剂量递增的两剂量方案，以确定该产品在人体中的安全性。第二阶段研究将比较最佳疫苗剂量下 2 剂或 3 剂的剂量方案。与第 2 期研究同时进行，免疫原性和功效研究将在气溶胶鼠疫攻击的非人灵长类动物模型中进行，以使用从第 1 期临床试验中选择的 Protollin-FIV 剂量，将鼻疫苗与铝佐剂肌肉注射 F1V 疫苗进行比较。