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) 的注射疫苗的市场接受度差和安全性问题，目前还没有针对由伯氏疏螺旋体引起的莱姆病的人类疫苗。保护人类免受莱姆病感染的另一种方法是对疾病宿主进行疫苗接种，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 疫苗可以成功地为啮齿动物接种疫苗，并降低蜱虫感染的流行率。我们的目标是开发一种新方法，通过使用源自稻谷的储库靶向疫苗 (RTV) 显着降低蜱载体肩突硬蜱的感染率，来预防人类接触莱姆病螺旋体。在 I 期 SBIR 中，我们证明可以在米粒中产生免疫原性 rOspA，并且通过针头注射 rOspA 免疫小鼠后，小鼠免受伯氏疏螺旋体攻击。在当前的第二阶段 SBIR 提案中，我们将通过多代田间选择开发稳定的水稻品系，为动物研究和未来商业化建立种子库。我们将通过口服给药在实验动物中测试 rOspA 对蜱肠道中伯氏疏螺旋体清除的有效性。最后，我们将进行现场测试，以确定流行地区受感染蜱虫数量的减少情况。由于稻谷天然是许多预计成为伯氏疏螺旋体宿主的动物的食物，因此在稻中生产 rOspA 比其他表达系统具有明显的优势，更重要的是，基于稻的 rOspA 将为人类提供出色的安全性。动物和环境。公共卫生相关性：莱姆病是由携带伯氏疏螺旋体的蜱虫叮咬引起的，是美国许多地区人类健康的主要威胁。先前的研究表明，通过用伯氏疏螺旋体的外表面蛋白 A 接种啮齿动物宿主疫苗，可以显着降低蜱中伯氏疏螺旋体的流行率。开发出一种负担得起的口服疫苗将使动物宿主大规模接种疫苗，并降低将莱姆病传播给人类的风险。