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: 7611034
• 负责人: NING HUANG
• 金额: $ 12.65万
• 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 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7611034
• 关键词: Animal Feed; Animals; Antigens; Area; Bite; Black-legged Tick; Borrelia burgdorferi; Canis familiaris; Cereals; Communities; Data; Development; Disease; Disease Reservoirs; Drug Formulations; Effectiveness; Environment; Exposure to; Food; Freeze Drying; Future; Generations; Growth; Health; Human; Immunity; In Vitro; Infection; Injectable; Insecta; Laboratories; Laboratory Animals; Lyme Disease; Marketing; Mus; Oral Administration; OspA protein; Peromyscus; Phase; Plants; Prevalence; Process; Production; Proteins; Recombinant Proteins; Research; Rice; Risk; Rodent; Safety; Seeds; Small Business Innovation Research Grant; Study Section; System; Testing; Ticks; Toxin; United States; Vaccinated; Vaccination; Vaccines; Vitamins; White-Footed Mouse; base; enzootic; exposed human population; feeding; large scale production; novel strategies; oral vaccine; prevent; protein expression; public health relevance; scale up; transmission process; vector; vector transmission

DESCRIPTION (provided by applicant): A vaccine for humans against Lyme disease caused by B. burgdorferi is currently not available due to market acceptance and safety of an injectable vaccine based on outer surface protein A (OspA). An alternate 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 studies have shown that orally administered OspA based vaccines successfully vaccinate rodents, and reduce prevalence of infection in ticks. In the present proposal, we plan 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. We will develop stable homozygous rice lines from our first generation transformants that can be used to produce rOspA for the present study and for future large scale production and community-wide distribution. We will formulate the rOspA and test the effectiveness of a reservoir targeting vaccine in laboratory animals. Finally, we will conduct purification and in vitro characterization of rOspA for use in future regulatory approval of rOspA based vaccines. 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和安全性，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。许多研究表明，口服施用的基于OspA的疫苗成功地对啮齿动物进行疫苗接种，并降低蜱中的感染率。在本提案中，我们计划开发一种新的方法来预防人类暴露于莱姆病螺旋体，通过使用来自水稻的储库靶向疫苗（RTV）显著降低蜱虫载体肩突硬蜱的感染率。我们将从我们的第一代转化体开发稳定的纯合水稻品系，其可用于生产rOspA用于本研究以及用于未来的大规模生产和全社区分布。我们将在实验室动物中配制rOspA并测试储库靶向疫苗的有效性。最后，我们将进行rOspA的纯化和体外表征，以用于将来基于rOspA的疫苗的监管批准。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。