Production of OspA in rice for the control of Lyme disease

在水稻中生产 OspA 用于控制莱姆病

• 批准号: 7999336
• 负责人: NING HUANG
• 金额: $ 45.52万
• 依托单位: VENTRIA BIOSCIENCE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7999336
• 关键词: Animal Feed; Animals; Antibodies; Area; Bite; Black-legged Tick; Borrelia burgdorferi; Canis familiaris; Cereals; Development; Disease; Disease Reservoirs; Drug Formulations; Effectiveness; Environment and Public Health; Epitopes; Exposure to; Flour; Food; Freeze Drying; Future; Generations; Growth; Health; Human; Immunity; Immunization; Infection; Injectable; Injection of therapeutic agent; Laboratory Animals; Laboratory mice; Lyme Disease; Marketing; Mus; Mutate; Needles; Oral; Oral Administration; OspA protein; Outcomes Research; Performance; Peromyscus; Phase; Plants; Population; Prevalence; Process; Production; Proteins; Recombinant Proteins; Recombinants; Research; Rice; Risk; Rodent; Route; Safety; Seeds; Serum; Site; Small Business Innovation Research Grant; System; Testing; Ticks; United States; Vaccinated; Vaccination; Vaccine Antigen; Vaccines; White-Footed Mouse; Work; base; commercialization; design; enzootic; exposed human population; feeding; field study; glycosylation; immunogenic; novel strategies; oral vaccine; prevent; protein expression; public health relevance; scale up; transmission process; vaccine effectiveness; vector

DESCRIPTION (provided by applicant): A vaccine for humans against Lyme disease caused by B. burgdorferi is currently not available due to poor market acceptance and safety concerns of an injectable vaccine based on outer surface protein A (OspA). An alternative approach to protecting humans from Lyme disease is to vaccinate the disease reservoirs to reduce or eliminate B. burgdorferi from vector ticks, thereby suppressing enzootic transmission and preventing them from passing the disease to humans. A number of lab studies have shown that orally administered OspA vaccines successfully vaccinate rodents, and reduce prevalence of infection in ticks. Our objective is to develop a novel approach for preventing human exposure to Lyme disease spirochetes by significantly reducing infection prevalence in the tick vector, Ixodes scapularis, using reservoir targeted vaccines (RTVs) derived from rice grain. In phase I SBIR, we demonstrate that we can produce immunogenic rOspA in rice grain and mice were protected from B. burgdoferi challenge after immunization with rOspA via needle injection. In the present Phase II SBIR proposal, we will develop stable rice lines via field selection in multiple generations to establish seed stock for animal study and for future commercialization. We will test the effectiveness of rOspA in laboratory animals via oral administration on clearance of B. burgdorferi in tick's gut. Finally, we will conduct a field test to determine the reduction of infected tick population in endemic area. Since rice grain is naturally a food of many of the animals expected to serve as B. burgdorferi reservoirs, producing rOspA in rice provides a distinct advantage over other expression systems and more importantly, rice-based rOspA will offer an excellent safety profile to humans, animals and the environment. PUBLIC HEALTH RELEVANCE: Lyme disease, caused by a bite from ticks carrying B. burgdorferi, is a major threat to human health in many areas of the United States. Previous studies show that the prevalence of B. burgdorferi in ticks can be dramatically reduced by vaccinating rodent reservoirs with outer surface protein A from B. burgdorferi. Development of an affordable oral vaccine would enable large scale vaccination of animal reservoirs, and decrease the risk of transmitting Lyme disease to humans.

描述(由申请人提供)：由于基于外表面蛋白A(OspA)的可注射疫苗的市场接受度较低和安全性问题，目前还没有针对由伯氏杆菌引起的莱姆病的人类疫苗。保护人类免受莱姆病侵袭的另一种方法是为病源接种疫苗，以减少或消除媒介蜱中的伯氏杆菌，从而抑制地方性传播，防止疾病传播给人类。许多实验室研究表明，口服OspA疫苗成功地接种了啮齿动物，并降低了扁虱的感染率。我们的目标是开发一种新的方法来预防人类接触莱姆病螺旋体，方法是使用从稻谷中提取的蓄水池靶向疫苗(RTV)，显著降低扁虱媒介肩部硬蜱的感染率。在第一阶段的SBIR中，我们证明了我们可以在大米中产生免疫原性的RoSPA，并且用RoSPA通过注射的方式免疫小鼠后，小鼠可以抵抗伯氏杆菌的攻击。在目前的第二阶段SBIR方案中，我们将通过多代田间选择培育稳定的水稻品系，为动物研究和未来的商业化建立种子储备。我们将在实验动物身上测试RoSPA的有效性，通过口服给药清除壁虱肠道中的伯氏杆菌。最后，我们将进行现场测试，以确定疫区被感染的硬蜱种群的减少情况。由于米粒自然是许多有望作为伯氏杆菌宿主的动物的食物，在大米中生产RoSPA比其他表达系统具有明显的优势，更重要的是，以大米为基础的RoSPA将对人类、动物和环境提供极好的安全性。 与公共卫生相关：莱姆病是由携带伯氏杆菌的扁虱叮咬引起的，在美国许多地区是对人类健康的主要威胁。先前的研究表明，通过给啮齿动物蓄水池接种伯氏芽孢杆菌外表面蛋白A，可以极大地降低勃氏芽孢杆菌在硬蜱中的流行率。开发一种负担得起的口服疫苗将使动物水库能够大规模接种疫苗，并降低将莱姆病传播给人类的风险。