Live Attenuated Oral Anthrax Vaccine

口服炭疽减毒活疫苗

• 批准号: 8101247
• 负责人: B. KIM LEE SIM
• 金额: $ 30万
• 依托单位: PROTEIN POTENTIAL, LLC
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8101247
• 关键词: Address; Adverse effects; Aerosols; Anthrax Vaccines; Anthrax disease; Antibiotic Resistance; Antibodies; Attenuated; Bacillus anthracis spore; Bacteria; Biological Assay; Bioterrorism; Categories; Collaborations; Cysteine; DNA Sequence Analysis; Development; Dose; Enzyme-Linked Immunosorbent Assay; Excision; Foundations; Freeze Drying; Genes; Genetic; Glycerol; Goals; Health; Health Professional; Individual; Infectious Agent; Injection of therapeutic agent; Licensing; Life; Mass Vaccinations; Methods; Mus; National Institute of Allergy and Infectious Disease; Needles; O Antigens; Oral; Organism; Phase; Phenotype; Plasmid Cloning Vector; Plasmids; Population; Preparation; Process; Production; Proteins; Recombinant DNA; Refrigeration; Reproduction spores; Route; Safety; Salmonella typhi; Seeds; Self-Administered; Sequence Analysis; Serum; Small Business Innovation Research Grant; Staging; Technology; Tryptophan; Typhoid Fever; Vaccines; Valine; Vial device; anthrax lethal factor; design; immunogenic; immunogenicity; microbial alkaline proteinase inhibitor; mouse model; oral vaccine; plasmid DNA; pressure; protective efficacy; rat Ran 2 protein; respiratory; response; stability testing; vaccination schedule; vaccine candidate; vector; weapons

DESCRIPTION (provided by applicant): Vaccines are a proven and effective approach for assuring widespread protection of large populations prior to or immediately following a bioterrorism attack. Our goal is to address two significant problems currently raised by bioterrorism threats: 1) the need for an easy method of mass vaccination and 2) the shortcomings of the current anthrax vaccine (NIAID "category A" agent) which requires needles and health professionals for administration, an extended vaccination schedule for protection (6 doses over 18 months) and the concern over adverse effects. To address this challenge, we have exploited the extensive safety record of the existing live, oral Salmonella Typhi Ty21a vaccine by utilizing it as a vector to develop a live oral vaccine carrier stably expressing rPA. We hypothesize that Ty21a is a suitable vaccine carrier for the stable expression of the rPA gene harbored on a low copy number plasmid. Further, we hypothesize that this vaccine can be formulated so that it will be safe, stable, and highly immunogenic and can be easily administered orally. The current proposal is aimed at completing the necessary final development steps (e.g. removal of antibiotic resistance gene from vector plasmid) and full characterization (genetic and microbiological) of the candidate prior to constructing a genetic seed bank and small-scale (5-10 liter) manufacture and lyophilization. Finally, the candidate will be studied for genetic stability, safety, immunogenicity and efficacy in a mouse model of anthrax disease. Successful completion of this Phase I SBIR will provide the foundation for development of an oral anthrax vaccine in a Phase II proposal, and for a platform technology for oral vaccines against multiple other infectious agents. PUBLIC HEALTH RELEVANCE: Anthrax bacteria produce spores that can be processed to become easily airborne. Vaccines are a proven and effective approach for assuring widespread protection of large populations prior to or immediately following a bioterrorism attack. Our goal is to address two significant problems currently raised by bioterrorism threats: 1) the need for an easy method of mass vaccination and 2) the shortcomings of the current anthrax vaccine (NIAID "category A" agent) which requires needles and health professionals for administration, an extended vaccination schedule for protection (6 doses over 18 months) and the concern over adverse effects. Further, we hypothesize that this vaccine can be formulated so that it will be safe, stable, and highly immunogenic and ultimately can be easily administered orally.

描述（由申请人提供）：疫苗是在生物恐怖主义攻击之前或之后立即确保大量人群的广泛保护的一种经过验证的有效方法。我们的目标是解决生物恐怖主义威胁当前引起的两个重大问题：1）需要简单的大规模疫苗接种方法； 2）当前炭疽疫苗的缺点（NIAID“类别A类”“特工”需要针头和卫生专业人员进行管理，以进行保护，以进行保护时间表（6剂在18个月内）（6次剂量）（6剂剂量），并具有不利影响。为了应对这一挑战，我们利用了现有的现场现场口服沙门氏菌Typhi Ty21a疫苗的广泛安全记录，利用它作为矢量来开发稳定表达RPA的现场口服疫苗载体。我们假设TY21A是用于在低拷贝数质粒上具有RPA基因稳定表达的稳定表达的合适疫苗载体。此外，我们假设可以配制这种疫苗，以使其安全，稳定且高度免疫原性，并且可以轻松地口服。当前的提案旨在完成必要的最终发展步骤（例如，从载体质粒中去除抗生素耐药性基因）和候选者的全面表征（遗传和微生物学），然后再构建遗传种子库和小规模（5-10升）的制造和冻干。最后，将研究候选人在炭疽病小鼠模型中的遗传稳定性，安全性，免疫原性和功效。成功完成I阶段I SBIR将为II期提案中口服炭疽疫苗的开发以及针对其他多种其他感染剂的口服疫苗的平台技术提供基础。 公共卫生相关性：炭疽细菌会产生可以加工的孢子，以容易空降。疫苗是在生物恐怖主义攻击之前或立即立即确保对大量人群进行广泛保护的一种经过验证和有效的方法。我们的目标是解决生物恐怖主义威胁当前引起的两个重大问题：1）需要简单的大规模疫苗接种方法； 2）当前炭疽疫苗的缺点（NIAID“类别A类”“特工”需要针头和卫生专业人员进行管理，以进行保护，以进行保护时间表（6剂在18个月内）（6次剂量）（6剂剂量），并具有不利影响。此外，我们假设可以配制这种疫苗，以便它具有安全，稳定和高度免疫原性，并且最终可以轻松地口服。