NASALLY-DELIVERED MUCOSAL SUBUNIT VACCINE FOR PLAGUE

经鼻递送的鼠疫粘膜亚单位疫苗

• 批准号: 6555570
• 负责人: CAROLE L. CRAMER
• 金额: $ 19.85万
• 依托单位: BIODEFENSE TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6555570
• 关键词: Yersinia pestis; Yersinia pestis disease; bacterial antigens; bacterial vaccines; bioterrorism /chemical warfare; genetically modified plants; immunomodulators; inhalation drug administration; laboratory mouse; mucosal immunity; plant extracts; recombinant proteins; tobacco; vaccine development; vector vaccine

DESCRIPTION (provided by applicant): We have developed a plant-based adjuvant/carrier:antigen fusion technology that offers significant advantages over conventional injectable vaccination regimes including: safety, mucosal efficacy, ease of delivery, rapid scalability, unlimited supply potential, and cost-savings. This technology has significant potential in contributing to biodefense strategies protecting both military and civilian populations currently threatened with biological weapons of mass destruction. Pneumonic plague is one of the most likely terrorist weapons for which no vaccine of proven efficacy is currently available. Since mucosal administration is considered the most effective route for conferring protection against a pneumonic form of the disease, the lack of an effective mucosal adjuvant acceptable for human use presents a significant hurdle. BioDefense Technologies, Inc. brings two new technologies to vaccine development that are significantly relevant for plague: 1) a new non-toxic mucosal adjuvant/carrier, MAC1, that functions to effectively deliver fused antigens to mucosal immune-responsive tissues and shows intranasal adjuvancy in mice equivalent to co-administered cholera toxin adjuvant and 2) transgenic plant-based bioproduction that addresses issues of safety, scale, and cost of recombinant subunit vaccines. A fusion of the Yersinia pestis protective antigens, F1 and V, appear the most promising for subunit vaccines. We propose to produce MAC1: F1:V fusion protein in transgenic tobacco. Purified MAC1:F1:V will be intranasally delivered to mice and mucosal and systemic responses will be used to assess vaccine efficacy. MAC1:F1:V adjuvancy in mice will be compared to that of co-administered F1:V and cholera toxin. These studies will provide the foundation for developing fusion proteins in transgenic plants, scale-up production protocols for MAC1:F1:V and conducting pneumonic plague challenges during Phase II. Our plant-based MAC1:antigen fusion technology is quite modular, easily purified and well suited for rapid development of new vaccines to counter genetically modified plague pathogens and newly emerging biowarfare agents. Furthermore, our MAC1:antigen technology has potential applications as a mucosal adjuvant/delivery molecule for developing non-defense related vaccines directed at HIV, cancer, and autoimmune diseases.

描述（由申请人提供）：我们开发了一种基于植物的辅助/载体：抗原融合技术，该技术比常规注射疫苗接种方案具有显着优势，包括：安全性，粘膜功效，易于交付，快速可扩展性，无限供应潜力和成本储备。 这项技术具有巨大的潜力，可以促进保护目前受到大规模杀伤性生物武器的军事和平民人口的生物化策略。 肺鼠疫是目前没有可靠的疗效疫苗的最可能的恐怖武器之一。 由于粘膜给药被认为是赋予对肺部疾病的肺炎形式保护的最有效途径，因此缺乏可用于人类使用的有效粘膜佐剂是一个很大的障碍。 Biodefense Technologies，Inc。为疫苗开发带来了与瘟疫显着相关的疫苗开发：1）一种新的无毒粘膜辅助/载体/载体MAC1，可有效地为粘膜提供融合的抗原，以使粘膜抗原与粘膜免疫 - 反应性组织和两种相对于固定性辅助效应，并显示出辅助辅助效果的内在辅助性，并表现基于植物的生物生产解决重组亚基疫苗的安全性，规模和成本问题。 耶尔森氏菌保护性抗原F1和V的融合似乎是亚基疫苗最有希望的。 我们建议在转基因烟草中产生Mac1：F1：V融合蛋白。 纯化的MAC1：F1：V将鼻内递送到小鼠，粘膜和全身反应将用于评估疫苗功效。 Mac1：F1：V将小鼠中的V佐剂与共同管理的F1：V和霍乱毒素的佐剂进行比较。 这些研究将为转基因植物中开发融合蛋白的基础，Mac1：F1：V的扩展生产方案以及在II期期间进行肺鼠疫挑战的基础。 我们基于植物的MAC1：抗原融合技术非常模块化，易于纯化，非常适合快速开发新的疫苗，以应对遗传改造的瘟疫病原体和新出现的生物质量剂。 此外，我们的MAC1：抗原技术具有潜在的应用作为粘膜辅助/递送分子，用于开发针对HIV，癌症和自身免疫性疾病的非防御相关疫苗。