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佐剂/载体：抗原融合技术，与传统的注射疫苗接种方案相比具有显着优势，包括：安全性、粘膜功效、易于递送、快速可扩展、无限的供应潜力和成本-储蓄。 这项技术在促进生物防御战略方面具有巨大潜力，可以保护目前受到大规模杀伤性生物武器威胁的军事和平民。 肺鼠疫是最有可能的恐怖武器之一，目前还没有经过证实有效的疫苗。 由于粘膜施用被认为是针对肺炎形式的疾病提供保护的最有效途径，因此缺乏可供人类使用可接受的有效粘膜佐剂存​​在重大障碍。 BioDefense Technologies, Inc. 为疫苗开发带来了两项与鼠疫密切相关的新技术：1) 一种新型无毒粘膜佐剂/载体 MAC1，其功能是将融合抗原有效递送至粘膜免疫反应组织，并显示鼻内佐剂作用在小鼠中，相当于共同施用霍乱毒素佐剂；2）基于转基因植物的生物生产，解决重组亚单位疫苗的安全性、规模和成本问题。 鼠疫耶尔森氏菌保护性抗原 F1 和 V 的融合似乎最有希望用于亚单位疫苗。 我们建议在转基因烟草中生产 MAC1:F1:V 融合蛋白。 纯化的 MAC1:F1:V 将鼻内递送至小鼠，粘膜和全身反应将用于评估疫苗功效。 将 MAC1:F1:V 佐剂在小鼠中的作用与同时施用 F1:V 和霍乱毒素的佐剂进行比较。 这些研究将为在转基因植物中开发融合蛋白、扩大 MAC1:F1:V 的生产方案以及在第二阶段进行肺鼠疫挑战奠定基础。 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疫苗，以对抗转基因鼠疫病原体和新兴的生物战剂。 此外，我们的 MAC1：抗原技术具有作为粘膜佐剂/递送分子的潜在应用，可用于开发针对 HIV、癌症和自身免疫性疾病的非防御相关疫苗。