A Novel Therapy for Staphyloccocal Enterotoxin B poisoning

描述（由申请人提供）：可食用疫苗受到了广泛关注，因为从理论上讲，它们代表了一种疫苗来源，可以刺激粘膜免疫反应，生产成本低，管理安全，并且可以稳定地运往世界各地。在这个STTR合作项目中提出的研究将开发一种口服疫苗，通过在转基因大豆中表达这种免疫原来对抗一种无毒形式的肠毒素葡萄球菌B （SEB）。由于SEB已被确定为生物恐怖主义的潜在媒介，而且目前尚无疫苗，因此完成此类研究将具有重要意义。此外，一旦生产出表达一种无毒形式的肠毒素B的转基因大豆，这些稳定转染的植物品系将永远成为这种可食用疫苗的可再生来源。在大豆中表达一种可食用的抗SEB无毒突变型的人疫苗的可行性和有效性将通过实现以下具体目标来完成。特异性目的1：在转基因大豆中表达一种免疫原，突变体SEB。本目的目的是表征SEB突变形式在用于口服疫苗的豆浆制剂中的表达。具体目的2：确定大豆衍生SEB作为粘膜免疫原口服给药后的疗效。在特定的目标#2中，我们将研究SEB在转基因大豆植物中的表达是否可以在小鼠口服免疫后引起高水平的免疫。这些研究的结果将确定接种这种可食用疫苗后B淋巴细胞和T淋巴细胞反应的大小。此外，将在小鼠模型中测试这种可食用疫苗制剂对SEB毒素攻击的保护能力。综上所述，这些研究将代表在转基因大豆中表达的可食用疫苗的使用取得了重大的实际进展。此外，这种可再生资源的可用性将为未来的第二阶段研究提供产品。

DESCRIPTION (provided by applicant): Edible vaccines have received much attention since, in theory, they represent a source of vaccine that would stimulate mucosal immune responses, be cost-effective to produce, be safe to administer, and be stable to ship throughout the world. Studies proposed in this collaborative STTR effort will develop an oral vaccine against a non-toxic form of Staphylococcus enterotoxin B (SEB) by expressing this immunogen in transgenic soybeans. Completion of such studies will be significant since SEB has been identified as a potential agent of bioterrorism, and since no vaccine is presently available. Furthermore, once transgenic soybeans expressing a non-toxic form of enterotoxin B have been produced, these stably transfected plant lines will forever be a renewable source of this edible vaccine. A demonstration of the feasibility and efficacy of expressing an edible human vaccine against a non-toxic, mutant form of SEB in soybeans will be accomplished by performing the following specific aims. Specific aim #1: Expression of an immunogen, mutant SEB, in transgenic soybeans. The purpose of this aim is to characterize expression of a mutant form of SEB in soy milk formulations for use in an oral vaccine. Specific aim #2: To determine the efficacy of soybean-derived SEB as a mucosal immunogen following oral administration. In specific aim #2, we will address whether expression of SEB in transgenic soybean plants can elicit high levels of immunity following oral immunization of mice. Results from these studies will determine the magnitude of the B and T lymphocyte responses following administration of this edible vaccine. In addition, the ability of this edible vaccine formulation to protect against an SEB toxin challenge in a mouse model will be tested. Taken together, these studies will represent a significant, practical advance for the use of edible vaccines that are expressed in transgenic soybeans. In addition, the availability of this renewable resource will provide a product for future Phase II studies.