A Novel Therapy for Staphyloccocal Enterotoxin B poisoning

治疗葡萄球菌肠毒素 B 中毒的新疗法

• 批准号: 7271825
• 负责人: KENNETH J PILLER
• 金额: $ 20.1万
• 依托单位: SOYMEDS, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-15 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7271825
• 关键词: Address; Adjuvant; Animal Model; Antigens; Attention; Bioterrorism; Categories; Clinical Trials; Coupled; Drug Formulations; Eating; Edible Vaccines; Effectiveness; Enterotoxins; Future; Glycine max; Human; Immune response; Immunity; Immunization; Licensing; Methods; Modeling; Mucosal Immune Responses; Mus; North Carolina; Oral; Oral Administration; Outcome; Pathology; Phase; Phase II Clinical Trials; Plants; Poisoning; Production; Purpose; Research Personnel; Resources; Seeds; Shipping; Ships; Small Business Technology Transfer Research; Source; Soy Milk; Soybeans; Staphylococcal Enterotoxin B; Staphylococcal Infections; Subunit Vaccines; T-Lymphocyte; Technology; Testing; Toxin; Transgenic Organisms; Transgenic Plants; Universities; Vaccines; Work; concept; cost; efficacy trial; immunogenicity; mouse model; mutant; novel; oral vaccine; protein expression; research and development; response; success; theories

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.

描述（由申请人提供）：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，可以刺激粘膜免疫应答，生产成本低，给药安全，并且在世界范围内运输稳定。在这项合作STTR努力中提出的研究将通过在转基因大豆中表达这种免疫原来开发针对无毒形式的葡萄球菌肠毒素B（SE B）的口服疫苗。由于SEB已被确定为潜在的生物恐怖主义制剂，而且目前还没有疫苗，因此完成这些研究将具有重要意义。此外，一旦产生了表达无毒形式的肠毒素B的转基因大豆，这些稳定转染的植物系将永远是这种可食用疫苗的可再生来源。通过实施以下具体目标，将实现在大豆中表达针对SEB的无毒突变形式的可食用人疫苗的可行性和功效的证明。具体目标#1：在转基因大豆中表达免疫原突变体SEB。该目的的目的是表征SEB的突变形式在用于口服疫苗的豆奶制剂中的表达。具体目标#2：确定大豆来源的SEB作为粘膜免疫原在口服给药后的功效。在具体目标#2中，我们将解决在转基因大豆植物中表达SEB是否可以在小鼠口服免疫后引发高水平的免疫。这些研究的结果将确定接种该可食用疫苗后B和T淋巴细胞应答的幅度。此外，将测试该可食用疫苗制剂在小鼠模型中保护免受SEB毒素攻击的能力。总之，这些研究将代表一个重要的，实际的进展，使用可食用的疫苗，表达在转基因大豆。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。

项目成果

Systemic cytokine and chemokine responses in immunized mice challenged with staphylococcal enterotoxin B.

用葡萄球菌肠毒素 B 攻击的免疫小鼠的全身细胞因子和趋化因子反应。

• DOI: 10.1016/j.toxicon.2017.05.005
• 发表时间: 2017
• 期刊: Toxicon : official journal of the International Society on Toxinology
• 作者: HudsonReichenberg,LauraC;Garg,Renu;Fernalld,Raymond;Bost,KennethL;Piller,KennethJ
• 通讯作者: Piller,KennethJ