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

• 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
• 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

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.

描述（由申请人提供）：疫苗提供了一种合理的方法，以确保在生物恐怖袭击之前或之后立即保护大人群。我们的目标I解决了生物恐怖主义威胁目前引起的三个重大问题：1）需要一种简单的大规模疫苗接种方法； 2）当前需要针头和卫生专业人员进行行政的炭疽疫苗的缺点，需要扩大疫苗接种时间表（在18个月内进行6剂6剂），并且担心不良影响； 3）缺乏在美国许可的瘟疫疫苗。为了应对这一挑战，我们将利用现有的现场直播，伤寒疫苗Ty21a的广泛安全记录，以及我们在工程方面的经验来表达炭疽芽孢杆菌的保护性抗原（PA），并诱导这种ty21A-Anthrax-antharax Pa vicine ty21a-ainthrax pa vicine ty21a-ainthrax aerthrax eerososol挑战。我们将利用TY21A作为向量开发多价组合口服疫苗，该疫苗将同时预防炭疽和瘟疫。此外，我们假设该疫苗可以配制为安全，稳定，高度免疫原性，并且可以容易口服。当前的应用旨在完成必要的最终疫苗结构，动物免疫原性和功效研究以及最终候选者的全面表征（遗传，免疫学，微生物学）。然后，我们将构建主细胞库，按照当前的良好制造实践进行小规模（10升）制造，并干燥产品以使温度稳定性和配方迅速溶解。将研究最终的疫苗制剂，以实现遗传稳定性，安全性，免疫原性 炭疽病和瘟疫疾病的小鼠，兔子和/或大鼠模型中的功效。 1临床试验以及该项目所有研究后随后的IND准备和提交。