Development of Enabling Vector/Antigen Expression Technology for an Orally-Delive

用于口服给药的载体/抗原表达技术的开发

基本信息

批准号：
8653932
负责人：
B. KIM LEE SIM
金额：
$ 110.03万
依托单位：
PROTEIN POTENTIAL, LLC
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-05-01 至 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8653932
关键词：
Address Adverse effects Aerosols Animals Anthrax Vaccines Anthrax disease Antigens Bioterrorism Clinical Trials Combined Vaccines Contractor Cyclic GMP Development Disease Dose Drug Formulations Engineering Genetic Genetic Identity Genetic Techniques Genomics Glycerol Goals Grant Health Professional Immunization Immunologic Techniques Individual Lead Licensing Life Mass Vaccinations Methods Microbiological Techniques Modeling Mus Mutation Needles Oral Organism Oryctolagus cuniculus Plague Plague Vaccine Plasmids Population Preparation Production Rattus Recombinants Regimen Safety Staging Technology Temperature Toxic effect Typhoid Fever United States Vaccines Vial device anthrax protective factor cell bank design experience immunogenic immunogenicity oral vaccine pre-clinical protective efficacy vaccination schedule vaccine candidate vector

项目摘要

DESCRIPTION (provided by applicant): Vaccines provide a rational approach for assuring protection of large populations prior to or immediately following a bioterrorism attack. Our goal i to address three significant problems currently raised by bioterrorism threats: 1) need for an easy method of mass vaccination; 2) shortcomings of the current anthrax vaccine which requires needles and health professionals for administration, requires an extended vaccination schedule (6 doses over 18 months) and has concerns over adverse effects; and 3) the lack of a plague vaccine licensed in the United States. To address this challenge, we will exploit the extensive safety record of the existing live, oral typhoid fever vaccine, Ty21a, and our experience in engineering it to express the protective antigen (PA) of Bacillus anthracis, and to induce protection against lethal anthrax aerosol challenge in mice with this Ty21a-anthrax PA vaccine. We will utilize Ty21a as a vector to develop a multi-valent combination oral vaccine that will simultaneously protect against anthrax and plague. Further, we hypothesize that this vaccine can be formulated to be safe, stable, highly immunogenic and can be easily administered orally. The current application is aimed at completing the necessary final vaccine constructions, animal immunogenicity and efficacy studies, and full characterization (genetic, immunological, microbiological) of the final candidates. We will then construct master cell banks, conduct small-scale (10 liter) manufacture in compliance with current Good Manufacturing Practices, and dry the product for temperature stability and formulation into rapidly dissolvable wafers. The final vaccine preparation will be studied for genetic stability, safety, immunogenicity and efficacy in mouse, rabbit, and/or rat models of anthrax and plague disease. 1 clinical trial, and subsequent IND preparation and submission after all studies in this project have been completed.