Development of an Oral Anthrax Vaccine

口服炭疽疫苗的开发

• 批准号: 6555511
• 负责人: John M Hilfinger
• 金额: $ 20.36万
• 依托单位: TSRL, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-15 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6555511
• 关键词: Bacillus anthracis; Peyer's patches; aluminum; anthrax; anthrax vaccines; bacterial antigens; bioterrorism /chemical warfare; dogs; dosage; drug delivery systems; hydroxides; immunomodulators; mucosal immunity; oral administration; vaccine development; vector vaccine

DESCRIPTION (provided by applicant): Of the numerous biological agents that may be used as weapons, the Working Group on Civilian Biodefense has identified Bacillus anthracis as one of the most serious agents. The most effective defense against this agent on a broad scale is through an aggressive vaccination program. Currently, there is one vaccine for use in the United States for anthrax, produced by the BioPort Corporation in Lansing Michigan. This vaccine is a filtrate from cultures of an avirulent, nonencapsulated strain of Bacillus anthracis which produces the protective antigen (PA) and that is adsorbed to aluminum hydroxide (termed anthrax vaccine adsorbed or AVA). With recent events foreshadowing broader usage of the vaccine in the general population, a more palatable formulation is necessary, one that will be equally if not more effective than the current vaccine. It is our hypothesis that oral delivery of the anthrax antigen will induce a robust mucosal and systemic immune response against the bacteria by selective targeting of intact antigens to the distal ileum Peyer's patches. Further, an oral vaccine has the benefits of ease of administration, with the likelihood of reduced adverse effects. This proposal will test the hypothesis that a potent antigen delivered intact to the distal ileum will induce a potent immune response. This strategy is supported by recent immunologic data and made possible by TSRL's emerging pharmaceutic technology, the PORT System Capsule -an innovative capsule-based system capable of delivering one or more timed doses of a drug in a single dosage form. Our ultimate goal for the phase 1 portion of this project will be an oral formulation that will elicit an immune response comparable to that of the FDA approved product, AVA, in the dog model. We feel that development of this technology for oral vaccines will have an immediate impact in the area of anthrax vaccine and will also have utility for a wide variety of other vaccines.

描述（由申请人提供）：在众多可用作武器的生物制剂中，民用生物防御工作组已将炭疽杆菌确定为最严重的制剂之一。 大规模对抗这种病原体的最有效防御方法是通过积极的疫苗接种计划。 目前，美国有一种炭疽疫苗使用，由密歇根州兰辛的 BioPort 公司生产。 该疫苗是无毒、无包膜的炭疽杆菌培养物的滤液，该菌株产生保护性抗原 (PA)，并被氢氧化铝吸附（称为吸附炭疽疫苗或 AVA）。 最近发生的事件预示着该疫苗将在普通人群中得到更广泛的使用，因此需要一种更适口的配方，这种配方即使不比现有疫苗更有效，也同样有效。 我们的假设是，口服炭疽抗原将通过选择性地将完整抗原靶向远端回肠派尔氏斑来诱导针对细菌的强大粘膜和全身免疫反应。 此外，口服疫苗具有易于给药的优点，并且可能减少不良反应。 该提案将检验以下假设：完整递送至远端回肠的有效抗原将诱导有效的免疫反应。 这一策略得到了最新免疫学数据的支持，并通过 TSRL 的新兴制药技术 PORT System Capsule 得以实现，这是一种基于胶囊的创新系统，能够以单一剂型输送一种或多种定时剂量的药物。 我们该项目第一阶段的最终目标是开发一种口服制剂，在狗模型中引发与 FDA 批准的产品 AVA 相当的免疫反应。 我们认为，口服疫苗这项技术的开发将对炭疽疫苗领域产生直接影响，并且也可用于多种其他疫苗。