An improved targeted vaccine strategy against anthrax

改进的针对炭疽的靶向疫苗策略

• 批准号: 6934232
• 负责人: Tibor P Keler
• 金额: $ 40.89万
• 依托单位: MEDAREX, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-15 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6934232
• 关键词: Macaca fascicularis; anthrax toxin; anthrax vaccines; antigen presenting cell; drug delivery systems; immunoconjugates; laboratory mouse; lectin; monoclonal antibody; neutralizing antibody; nonhuman therapy evaluation; vaccine development; vaccine evaluation

DESCRIPTION (provided by applicant): The long term goal of this proposal is to develop a novel targeted vaccine technology against emerging infectious diseases and pathogens associated with bioterrorism. Previous studies have documented the extremely rapid and potent immune responses elicited by vaccines that target antigens specifically to professional antigen presenting cells (APCs). In addition to induction of rapid and robust immune responses targeted vaccines have the potential to be safer, easily administered, and require very low doses for a more cost-effective product. We have developed a human monoclonal antibody (mAb) specific for mannose receptors (MRs) that are abundantly expressed on dendritic cells(DCs) and other APCs, as a delivery vehicle or antigen targeting. Antigens linked to this mAb are efficiently presented and induce potent antibody and cytotoxic T lymphocyte responses. In this application, we propose to develop and test a targeted vaccine for prevention and treatment of anthrax by attaching the anthrax protective antigen to our MR mAb. We hope to demonstrate induction of toxin neutralizing antibodies within days of immunization in rodents and primates, which will justify further development of the vaccine in spore challenge models. Vaccine efficacy will be assessed after intramuscular or nasal delivery using a well established toxin neutralization assay. Successful completion of the project would result in an easily administered, cost-effective vaccine that would be useful or the vaccination of individuals 1) suspected of exposure, 2) at high risk of near-term exposure, 3) and possibly after appearance of anthrax related symptoms. Such a vaccine could also greatly reduce the course of antibiotics that is currently given to potentially exposed individuals. Furthermore, in his vaccine would serve as a prototype for application of this technology to other important infectious disease pathogens where a fast acting vaccine is needed.

描述（由申请人提供）：该提案的长期目标是开发一种针对新出现的传染病和与生物恐怖主义相关的病原体的新型靶向疫苗技术。先前的研究已经记录了专门针对专业抗原呈递细胞（APC）的疫苗所引发的极其快速和有效的免疫反应。除了诱导快速和强大的免疫反应之外，靶向疫苗还具有更安全、更容易管理的潜力，并且需要非常低的剂量来获得更具成本效益的产品。我们开发了一种特异性针对在树突状细胞 (DC) 和其他 APC 上大量表达的甘露糖受体 (MR) 的人单克隆抗体 (mAb)，作为递送载体或抗原靶向。与该 mAb 连接的抗原被有效呈递并诱导有效的抗体和细胞毒性 T 淋巴细胞反应。在此应用中，我们建议通过将炭疽保护性抗原附着到我们的 MR mAb 上来开发和测试用于预防和治疗炭疽的靶向疫苗。我们希望在啮齿动物和灵长类动物中展示免疫后几天内诱导毒素中和抗体，这将证明在孢子攻击模型中进一步开发疫苗的合理性。肌肉注射或鼻腔给药后，将使用成熟的毒素中和测定来评估疫苗功效。该项目的成功完成将产生一种易于管理、具有成本效益的疫苗，该疫苗对 1) 疑似接触者、2) 近期接触高风险者、3) 以及可能出现炭疽病后的个体进行疫苗接种相关症状。这种疫苗还可以大大减少目前对潜在暴露个体使用的抗生素疗程。此外，他的疫苗将作为将该技术应用于需要速效疫苗的其他重要传染病病原体的原型。