Vaccination Against Ixodes scapularis Tick Bites

描述(由申请人提供)： 莱姆病是由伯氏疏螺旋体引起的一种多系统感染。黑腿硬蜱是伯氏白纹伊蚊的常见媒介。这种扁虱还传播人类粒细胞性埃立克体病和巴贝斯虫病的病原体。这个项目的目的是开发一种抗I。用于阻断壁虱附着和壁虱介导性疾病传播的肩铃虫疫苗。感染了我肩铃虫的兔子或豚鼠获得了抗体介导的对扁虱叮咬的抵抗力，这种现象被称为“扁虱免疫”。 第一阶段实验评估了Salp13和Salp25D，这两个重组蛋白表达于 1.肩关节唾液腺基因，作为候选疫苗。用这两种重组蛋白组合免疫的豚鼠表现出对扁虱叮咬的抵抗力。第二阶段的具体目标是：(A)生产适用于在动物模型中进行广泛测试的Salp 13和Salp25D疫苗原型；(B)调查Salp 13和Salp25D对被扁虱叮咬诱导的扁虱免疫的贡献；以及(C)确定优化的Salp13/Salp25D疫苗免疫是否能阻止蜱虫的病原体传播。这些实验将导致第三阶段开发一种新的疫苗，旨在预防多种壁虱传播的病原体。 建议的商业应用： 一种针对扁虱叮咬的疫苗可能会预防几种病原体，包括伯氏巴贝斯虫和人类粒细胞性埃立克体病的病原体。商业市场将与Lymerix、葛兰素史克公司的人类莱姆病疫苗和目前批准的犬莱姆病疫苗的市场重叠。

DESCRIPTION (provided by applicant): Lyme disease is a multi-systemic infection caused by the pathogen Borrelia burgdorjeri. The black-legged tick, Ixodes scapularis, is the common vector for B. burgdorferi. This tick also transmits the agents of human granulocytic ehrlichiosis and babesiosis. The purpose of this project is to develop an anti-I. scapiilaris vaccine to block tick attachment and tick-mediated disease transmission. Rabbits or guinea pigs infested with I. scapularis acquire antibody-mediated resistance to tick bites, a phenomenon known as "tick-immunity.'' Phase I experiments evaluated Salp13 and Salp25D, two recombinant proteins expressed from I. scapularis salivary gland cDNAs, as candidate vaccines. Guinea pigs immunized with a combination of the two recombinant proteins demonstrated host resistance to tick bites. Phase II specific aims are to: (a) produce prototype Salp 13 and Salp25D vaccines suitable for extensive testing in animal models; (b) investigate Salp 13 and Salp25D contributions to the tick bite-induced tick immunity; and (c) determine if immunization with an optimized Salp13/Salp25D vaccine blocks pathogen transmission from ticks. These experiments will lead to Phase III development of a new vaccine designed to protect against multiple tick-borne pathogens. PROPOSED COMMERCIAL APPLICATION: A vaccine against Ixodes scapiilaris tick bites would potentially protect against several pathogens, including B. burgdorferi, Babesia microti, and the agent of human granulocytic ehrlichiosis. The commercial market would overlap with the market for LYMErix, a Glaxo SmithKline human Lyme disease vaccine, and the currently approved canine Lyme disease vaccines.