Research Project
6845743
[unreadable] 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. [unreadable] [unreadable]
