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.

性状（由申请方提供）：产肠球菌E.大肠杆菌（ETEC）是发展中国家三岁以下儿童和前往这些地区的旅行者中的腹泻病的主要原因，每年有超过2亿例病例，38万例相关死亡。ETEC通过被粪便污染的食物或水传播，疾病的特征是持续数天至数周的大量水样腹泻。ETEC疾病的预防性预防目前不可用，并且已经出现了ETEC的耐药菌株。Triton Animal Products，Inc.正在开发一种治疗性蛋白质，乳腺相关血清淀粉样蛋白A3（MAA），可提供预防性保护，防止ETEC感染。MAA是存在于初乳（母乳的早期形式）中的口服活性、进化上保守的蛋白质。MAA是一种先天性免疫因子，可刺激肠上皮细胞分泌粘蛋白，从而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粘附和定殖。杆菌Triton的重组蛋白表达平台是一种绿色载体，可食用、廉价、可扩展且安全，因此无需昂贵的蛋白纯化。根据初步数据，我们估计藻类产生的MAA可以以大约4%/剂的价格制成。我们的技术将使旅行者、部署的服务人员和生活在发展中国家的高危儿童能够口服生物活性MAA，以降低ETEC疾病的发病率。断奶后猪将用作人ETEC疾病的动物模型，以确定预防感染的有效MAA剂量和给药时间。此外，我们还将研究第二代治疗药物--一种MAA和初乳中天然抗菌肽的基因融合物--它有可能提供预防感染的保护和抗菌活性 来预防和治疗疾病。