Vaccination Against Ixodes scapularis Tick Bites

描述（由申请人提供）： 莱姆病是由病原体伯氏疏螺旋体引起的多系统感染。黑腿蜱，肩突硬蜱，是B的常见媒介。burgdorferi。这种蜱也传播人类粒细胞埃里希体病和巴贝虫病的病原体。本项目的目的是开发一种抗I。scapiilaris疫苗阻断蜱附着和蜱介导的疾病传播。感染I.肩胛肌获得抗体介导的对蜱叮咬的抗性，这种现象称为"蜱免疫"。'' I期实验评估了Salp13和Salp25D，这两种重组蛋白表达自 I.肩胛肌唾液腺cDNA作为候选疫苗。用两种重组蛋白的组合免疫的豚鼠表现出对蜱叮咬的宿主抗性。II期的具体目标是：（a）生产适用于动物模型中广泛测试的Salp 13和Salp 25 D原型疫苗;（B）研究Salp 13和Salp 25 D对蜱叮咬诱导的蜱免疫的贡献;以及（c）确定用优化的Salp 13/Salp 25 D疫苗免疫是否阻断蜱的病原体传播。这些实验将导致一种新疫苗的第三阶段开发，该疫苗旨在预防多种蜱传病原体。 拟定商业应用： 一种针对硬蜱叮咬的疫苗可能会预防包括B在内的几种病原体。burgdorferi、Babeliamoti和人粒细胞埃里希体病的病原体。商业市场将与LYMErix市场重叠，LYMErix是Glaxo SmithKline人类莱姆病疫苗，目前已批准的犬莱姆病疫苗。

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.