Edible adjuvant expressed in transgenic soybeans

转基因大豆中表达的食用佐剂

• 批准号: 6814707
• 负责人: KENNETH L BOST
• 金额: $ 6.63万
• 依托单位: UNIVERSITY OF NORTH CAROLINA CHARLOTTE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6814707
• 关键词: Escherichia coli; bacterial proteins; biotechnology; cytoplasm; eating; enterotoxins; gene expression; genetically modified plants; immunologic substance development /preparation; immunomodulators; laboratory mouse; oral administration; plant extracts; protein quantitation /detection; seeds; soybeans; tetanus toxoid; vaccines

DESCRIPTION (provided by applicant): One of the most significant limitations faced when developing new vaccine formulations for human use is the lack of safe, efficacious adjuvants that can be combined with promising new vaccine candidates to stimulate a protective host response, in the absence of safe, efficacious adjuvants that can be combined with these new vaccine candidates, the vaccine, by itself, is often not sufficient to protect individuals from a particular microbial disease. This is especially true for the development of subunit vaccines that use a single protein isolated from a microbial pathogen in an attempt to protect individuals from viral, bacterial, or fungal pathogens. These subunit vaccines are often very safe since they do not cause any infection and since they have fewer side effects than attenuated or killed microbes sometimes used in vaccine formulations. However there is one significant limitation in using these safer subunit vaccines. By themselves, the microbial proteins often do a poor job at stimulating human immune responses unless a vaccine formulation containing a strong adjuvant is used, especially when trying to stimulate a protective, mucosal response. In this grant application, Drs. Bost, Piller and Clemente propose to demonstrate the feasibility of developing an edible adjuvant expressed in transgenic plants. These novel studies focus on the use of a known adjuvant, the E. coil heat labile toxin (LT), and its expression in soybeans. A non-toxic form of this bacterial protein, which has potent adjuvant activity, will be expressed in soybeans, and its ability to function as an adjuvant following oral consumption will be demonstrated using a mouse immunization model. If successful, this work will provide an efficient expression system for production of large quantities of an edible adjuvant which is cost-effective to produce, safe to administer, and could be shipped worldwide in a highly stable form (i.e. soybeans). The fact that extensive procedures for processing soybeans into human consumables already exist suggest that this work could be readily translated to the production of a plant derived, edible adjuvant useful in novel human vaccine formulations.

说明(申请人提供)：开发供人类使用的新疫苗配方时面临的最大限制之一是缺乏安全、有效的佐剂，这些佐剂可以与有希望的新候选疫苗结合来刺激保护性宿主反应，在没有安全、有效的佐剂可以与这些新的候选疫苗结合的情况下，疫苗本身往往不足以保护个人免受特定微生物疾病的影响。这对于亚单位疫苗的开发尤其如此，这种疫苗使用从微生物病原体分离的单一蛋白，试图保护个人免受病毒、细菌或真菌病原体的侵袭。这些亚单位疫苗通常是非常安全的，因为它们不会引起任何感染，而且它们的副作用比疫苗配方中有时使用的减毒或杀死的微生物更少。然而，使用这些更安全的亚单位疫苗有一个显着的限制。微生物蛋白本身在刺激人类免疫反应方面往往做得很差，除非使用含有强佐剂的疫苗配方，特别是在试图刺激保护性的粘膜反应时。 在这项拨款申请中，Bost、Piller和Clemente博士建议证明开发一种在转基因植物中表达的可食用佐剂的可行性。这些新的研究集中在一种已知的佐剂的使用，即E.coil热不稳定毒素(LT)，及其在大豆中的表达。这种细菌蛋白的一种无毒形式，具有强大的佐剂活性，将在大豆中表达，并将使用小鼠免疫模型证明其在口服后作为佐剂的能力。如果成功，这项工作将提供一种高效的表达系统，用于生产大量的可食用佐剂，这种佐剂生产成本低，给药安全，并可以以高度稳定的形式运往世界各地(即大豆)。将大豆加工成人类消耗品的广泛程序已经存在，这一事实表明，这项工作很容易转化为生产一种用于新型人类疫苗配方的植物来源的可食用佐剂。