Algae-expressed colostrum protein as prophylaxis for enterotoxigenic E. coli

藻类表达的初乳蛋白可预防产肠毒素大肠杆菌

• 批准号: 8715521
• 负责人: Beth Rasala
• 金额: $ 15万
• 依托单位: TRITON ALGAE INNOVATIONS, INC
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8715521
• 关键词: Adherence; Adhesions; Affect; Age-Years; Algae; Amyloid; Animal Model; Animals; Antibiotic Resistance; Antibiotics; Antibodies; Area; Bacteria; Bacterial Infections; Beverages; Birth; Breast Feeding; Categories; Centers for Disease Control and Prevention (U.S.); Cessation of life; Child; Chimeric Proteins; Colostrum; Data; Developing Countries; Diarrhea; Disease; Dose; Enteral; Enterobacteriaceae; Enterotoxins; Epithelial Cells; Escherichia coli; Escherichia coli EHEC; Escherichia coli Infections; Family suidae; Feces; Fluids and Secretions; Food; Gastrointestinal tract structure; Generations; Genetic; Gram-Negative Bacteria; Green Algae; Heating; Host Defense; Hour; Human; Human Milk; Immune; In Vitro; Incidence; Infant; Infection; Infection prevention; Intestines; Lactoferrin; Legal patent; Life; Mammary gland; Marketing; Milk; Mucins; Oral; Oral Administration; Organism; Pepsin A; Prevalence; Prevention; Production; Prophylactic treatment; Proteins; Recombinant Proteins; Recombinants; Risk; Schedule; Scheme; Serum; Services; Small Intestines; Stomach; Technology; Testing; Therapeutic; Time; Toxin; Triton; Tritons; United States; Vaccines; Visit; Water; Weaning; World Health Organization; antimicrobial; antimicrobial peptide; base; cell killing; enteroaggregative Escherichia coli; enteroinvasive Escherichia coli; enteropathogenic Escherichia coli; enterotoxigenic Escherichia coli; human disease; member; microorganism; natural antimicrobial; neonate; next generation; novel strategies; pathogenic Escherichia coli; pathogenic bacteria; prevent; prophylactic; protective effect; protein expression; protein purification; public health relevance; purge; resistant strain; therapeutic protein

DESCRIPTION (provided by applicant): Enterotoxigenic E. coli (ETEC) is the leading cause of diarrheal disease among children less than three years of age in developing countries and in travelers to these areas, with over 200 million cases annually, and 380,000 associated deaths. ETEC is transmitted by food or water contaminated with feces, and illness is characterized by profuse watery diarrhea lasting for several days to weeks. Prophylactic prevention of ETEC disease is currently unavailable, and antibiotic-resistant strains of ETEC have emerged. Triton Animal Products, Inc. is developing a therapeutic protein, mammary-associated serum amyloid A3 (MAA) that may offer prophylactic protection against ETEC infections. MAA is an orally-active, evolutionarily conserved protein present in colostrum - an early form of breast milk. MAA is an innate immune factor that stimulates intestinal epithelial cells to secrete mucin, which provides a natural protective barrier that inhibits adherence and colonization of enteropathogens, including E. coli. Triton's recombinant protein expression platform, a green alga, is edible, inexpensive, scalable, and safe, thus negating the need for expensive protein purification. Based on preliminary data, we estimate that algal-produced MAA can be made for approximately 4cent per dose. Our technology will enable the oral delivery of bioactive MAA to travelers, deployed service members, and at-risk children living in developing countries, to reduce the incidence of ETEC disease. Post-weaned pigs will be used as an animal model for human ETEC disease to determine effective MAA dosing and timing of administration for the prevention of infections. Furthermore, we will investigate a second- generation therapeutic - a genetic fusion between MAA and a natural antimicrobial peptide also present in colostrum - that has the potential to offer both prophylactic protection from infection and antimicrobial activities to prevent and treat disease.

说明(申请人提供)：产肠毒素大肠杆菌(ETEC)是发展中国家和前往这些地区的旅行者中三岁以下儿童腹泻疾病的主要原因，每年有2亿多例病例，38万人相关死亡。ETEC通过被粪便污染的食物或水传播，疾病的特点是大量水样腹泻，持续几天到几周。目前尚不能预防性预防ETEC病，出现了ETEC耐药株。Triton Animal Products，Inc.正在开发一种治疗性蛋白质--乳房相关血清淀粉样蛋白A3(MAA)，它可能对ETEC感染提供预防性保护。MAA是一种口服活性的、进化上保守的蛋白质，存在于初乳中--初乳是母乳的早期形式。MAA是一种先天免疫因子，刺激肠道上皮细胞分泌粘蛋白，粘蛋白提供一种天然的保护屏障，抑制包括大肠杆菌在内的肠道病原体的黏附和定植。Triton的重组蛋白表达平台-绿藻-可食用、廉价、可扩展和安全，因此不需要昂贵的蛋白质纯化。根据初步数据，我们估计每剂藻类产生的MAA约为4美分。我们的技术将使生物活性MAA能够口服给生活在发展中国家的旅行者、部署的服务人员和高危儿童，以减少ETEC疾病的发生率。断奶后的猪将被用作人类ETEC疾病的动物模型，以确定预防感染的有效MAA剂量和给药时机。此外，我们将研究第二代治疗方法--MAA和一种同样存在于初乳中的天然抗菌肽之间的基因融合--它具有预防感染和抗菌活性的潜力。 预防和治疗疾病。