Vaccination Against Ixodes scapularis Tick Bites

肩胛硬蜱蜱叮咬疫苗接种

• 批准号: 6337782
• 负责人: Raymond Allen Koski
• 金额: $ 9.96万
• 依托单位: L2 DIAGNOSTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-15 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6337782
• 关键词: Borrelia; Ixodes; Lyme disease; active immunization; arthropod borne communicable disease; bacterial antigens; bacterial vaccines; borreliosis; guinea pigs; host organism interaction; laboratory rabbit; protein purification; recombinant proteins; vaccine development; vector vaccine

Lyme disease is a multi-systemic infection and is caused by the pathogen Borrelia burgdorferi. The blacklegged tick, Ixodes scapularis, is the common vector for B. burgdorferi. The purpose of this project is to develop an anti-I. scapularis 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." We have developed a guinea pig model of host immunity against ticks. The tick-sensitized guinea pigs do not acquire Lyme disease when challenged with B. burgdorferi-infected I.. scapularis. Our plan is to determine which tick salivary gland antigens confer such host immunity, and subsequently produce them as recombinant antigens for evaluation as candidate vaccines. In preliminary experiments two recombinant proteins expressed from I. scapularis salivary gland cDNAs, Salp13 and Salp25D, induced tick-immunity. Phase I research will produce the recombinant proteins in prokaryotic and eukaryotic I expression systems. Guinea pigs and rabbits will be immunized with the purified antigens. We will then demonstrate host resistance to ticks, and inhibition of B. burgdorferi transmission from infected ticks. These experiments will lead to Phase II development of new vaccines to protect against multiple tick-borne pathogens. PROPOSED COMMERCIAL APPLICATIONS: A vaccine against Ixodes scapularis tick bites would potentially protect against several pathogens, including B. burgdorferi, the agent of human granulocytic ehrlichiosis, and Babesia microti. The commercial market would overlap with the market for LYMErix, a Lyme disease vaccine successfully sold by SmithKline Beecham.

莱姆病是一种多系统感染，由病原体伯氏疏螺旋体引起。黑腿蜱（Ixodes scapularis）是伯氏疏螺旋体的常见媒介。该项目的目的是开发一种抗I。肩胛肌疫苗可阻止蜱附着和蜱介导的疾病传播。 。感染了肩胛 I. scapularis 的兔子或豚鼠获得了抗体介导的对蜱叮咬的抵抗力，这种现象被称为“蜱免疫”。我们开发了一种针对蜱虫宿主免疫的豚鼠模型。当受到伯氏疏螺旋体感染的肩胛疏螺旋体攻击时，对蜱敏感的豚鼠不会感染莱姆病。我们的计划是确定哪些蜱唾液腺抗原赋予这种宿主免疫力，然后将它们生产为重组抗原，以作为候选疫苗进行评估。在初步实验中，两种从肩突蜱唾液腺 cDNA 表达的重组蛋白 Salp13 和 Salp25D 诱导了蜱免疫。 I 期研究将在原核和真核 I 表达系统中生产重组蛋白。将用纯化的抗原免疫豚鼠和兔子。然后，我们将证明宿主对蜱的抵抗力，以及对受感染蜱传播伯氏疏螺旋体的抑制作用。这些实验将导致新疫苗的二期开发，以预防多种蜱传病原体。拟议的商业应用：针对肩胛硬蜱叮咬的疫苗可能可以预防多种病原体，包括伯氏疏螺旋体（人类粒细胞埃利希体病的病原体）和田鼠巴贝斯虫。商业市场将与 LYMErix 市场重叠，LYMErix 是 SmithKline Beecham 成功销售的莱姆病疫苗。