NASALLY-DELIVERED MUCOSAL SUBUNIT VACCINE FOR PLAGUE

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，该技术提供了优于常规注射疫苗接种方案的显著优势，包括：安全性、粘膜功效、易于递送、快速可扩展性、无限供应潜力和成本节约。 这项技术在促进生物防御战略方面具有巨大潜力，可保护目前受到大规模毁灭性生物武器威胁的军事和平民。 鼠疫是最有可能的恐怖主义武器之一，目前没有证明有效的疫苗。 由于粘膜给药被认为是提供针对肺炎形式的疾病的保护的最有效途径，因此缺乏人使用可接受的有效粘膜佐剂是一个重大障碍。 BioDefense Technologies，Inc.为疫苗开发带来了两项与鼠疫显著相关的新技术：1）一种新的无毒粘膜佐剂/载体，MAC 1，其功能是有效地将融合抗原递送至粘膜免疫应答组织，并在小鼠中显示出与共同施用的霍乱毒素佐剂相当的鼻内免疫力，以及2）基于转基因植物的生物生产，其解决了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的融合体似乎是最有希望的亚单位疫苗。 我们拟在转基因烟草中生产MAC 1：F1：V融合蛋白。 纯化的MAC 1：F1：V将鼻内递送至小鼠，粘膜和全身反应将用于评估疫苗有效性。 将在小鼠中的MAC 1：F1：V效力与共同施用的F1：V和霍乱毒素效力进行比较。 这些研究将为在转基因植物中开发融合蛋白、扩大MAC 1：F1：V的生产方案以及在第二阶段进行肺鼠疫挑战提供基础。 我们基于植物的MAC 1：抗原融合技术是相当模块化的，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出现的生物战剂。 此外，我们的MAC 1：抗原技术具有潜在的应用，可作为粘膜佐剂/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。

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.