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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

基本信息

批准号：
8296677
负责人：
NING HUANG
金额：
$ 28.66万
依托单位：
VENTRIA BIOSCIENCE
依托单位国家：
美国
项目类别：
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/8296677
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

项目摘要

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差和安全性问题，目前无法获得由伯氏疏螺旋体引起的人类莱姆病疫苗。保护人类免受莱姆病侵害的另一种方法是为疾病宿主接种疫苗，以减少或消除媒介蜱中的伯氏疏螺旋体，从而抑制地方性动物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疫苗成功地为啮齿动物接种了疫苗，并减少了蜱虫感染的流行。我们的目标是开发一种新的方法，通过使用源自稻谷的水库靶向疫苗（RTVs）显著降低蜱媒介肩胛骨伊蚊的感染率，来预防人类接触莱姆病螺旋体。在I期SBIR中，我们证明了我们可以在稻谷中产生免疫原性rOspA，并且通过针注射rOspA免疫小鼠后可以保护小鼠免受伯氏疏螺旋体的攻击。在目前的第二阶段SBIR提案中，我们将通过多代的田间选择来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储备。我们将在实验动物中通过口服给药来测试rOspA对蜱肠道内伯氏疏螺旋体的清除效果。最后，我们将进行实地试验，以确定疫区受感染蜱虫种群的减少情况。由于水稻是许多动物的天然食物，有望成为伯氏疏螺旋体的宿主，因此在水稻中生产rOspA比其他表达系统具有明显的优势，更重要的是，基于水稻的rOspA将为人类，动物和环境提供良好的安全性。