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（由申请人提供）：目前由于基于外表面蛋白A（OSPA）的可注射疫苗的市场接受和安全性，目前尚无针对由B. burgdorferi引起的针对莱姆病的疫苗。保护人类免受莱姆病的另一种方法是为疾病疫苗接种疫苗，以减少或消除B. burgdorferi免受矢量滴答的速度，从而抑制Enzootic的传播并防止其将疾病传递给人类。许多研究表明，口服基于OSPA的疫苗成功接种啮齿动物，并降低了壁虱感染的患病率。在本提案中，我们计划通过使用储层靶向疫苗（RTV）来显着降低tick载体Ixodes capapularis的感染率，从而开发一种新的方法来防止人类暴露于莱姆病螺旋体。我们将从第一代转化器中开发稳定的纯合稻线，这些稻米可用于本研究以及未来的大规模生产和社区范围的分布来生产ROSPA。我们将制定ROSPA，并测试靶向疫苗在实验动物中的有效性。最后，我们将对ROSPA进行纯化和体外表征，以用于将来的基于ROSPA的疫苗的调节批准。由于水稻颗粒自然是许多预期用作B. burgdorferi储层的动物的食物，因此在大米中产生Rospa比其他表达系统具有明显的优势，更重要的是，基于稻米的Rospa将为人类，动物和环境提供出色的安全性。公共卫生相关性：由携带B. burgdorferi的tick虫的咬伤引起的莱姆病是美国许多地区对人类健康的主要威胁。先前的研究表明，通过用B. burgdorferi的外表面蛋白A疫苗接种啮齿动物储层，可以大大降低滴答虫中的爆发芽孢杆菌的患病率。负担得起的口服疫苗的开发将使动物储层的大规模疫苗接种，并降低将莱姆病传播给人类的风险。