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: 8101241
• 负责人: NING HUANG
• 金额: $ 29.69万
• 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/8101241
• 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; 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（由申请方提供）：一种用于预防由B引起的莱姆病的人类疫苗。由于基于外表面蛋白A（OspA）的可注射疫苗的市场接受度差和安全性问题，目前还不能获得伯氏螺旋体。保护人类免受莱姆病的另一种方法是接种疾病宿主以减少或消除B。从媒介蜱中分离出伯氏螺旋体，从而抑制地方性传播并防止它们将疾病传播给人类。许多实验室研究表明，口服OspA疫苗可成功地对啮齿动物进行疫苗接种，并降低蜱虫感染的患病率。我们的目标是开发一种新的方法来预防人类暴露于莱姆病螺旋体，显着降低感染率的蜱媒介，肩突硬蜱，使用水库靶向疫苗（RTVs）来自水稻谷物。在I期SBIR中，我们证明了我们可以在稻米中产生免疫原性rOspA，并且小鼠免受B的侵害。在用rOspA通过针注射免疫后进行伯氏菌攻击。在目前的第二阶段SBIR提案中，我们将通过多代田间选择开发稳定的水稻品系，以建立用于动物研究和未来商业化的种子库。我们将在实验室动物中通过经口给药检测rOspA对B清除的有效性。蜱虫肠道里的伯氏菌最后，我们将进行实地测试，以确定在流行地区减少受感染的蜱虫种群。因为稻米是许多动物的食物，所以被认为是B。在Burgdorferi宿主中，在水稻中产生rOspA提供了优于其他表达系统的明显优势，更重要的是，基于水稻的rOspA将为人类、动物和环境提供优异的安全性。 公共卫生相关性：莱姆病，由携带B的蜱叮咬引起。burgdorferi是美国许多地区对人类健康的主要威胁。以往的研究表明，B。通过用来自B的外表面蛋白A接种啮齿动物宿主可以显著降低蜱中的伯氏螺旋体。burgdorferi。开发负担得起的口服疫苗将能够大规模接种动物宿主，并降低莱姆病传播给人类的风险。