TICK SALIVA AND LYME DISEASE AND VACCINE STRATEGY

带菌者唾液似乎在成功的 吸血的节肢动物的吸血。唾液的成分 增强病原体传播和宿主感染。最近关于 肩胛硬蜱唾液的药理学性质， 美国东部莱姆病螺旋体的主要媒介，揭示 它的唾液中含有增强吸血的物质， 决定了向量的能力。特别是，抗补体活性， 这种蜱的唾液可以提供保护， 杀死伯氏疏螺旋体和宿主排斥蜱。在 此外，唾液组分改变B中的蛋白质表达。burgdorferi， 也许会增强这种细菌的传染性， 宿主对感染的反应本研究将：（一）确定 并对I.肩胛肌唾液 抗补体活性，并影响B中的蛋白质表达。 （2）评估蜱唾液组分的保护作用 收集自各种硬蜱（例如I.肩胛肌，革蜱 variabilis，Amhlyomma americanum）在B.基于互补的burgdorferi （3）确定蜱唾液对蛋白质的影响 在B中表达。以及对宿主免疫应答的影响; (4)评价B的致病性和侵袭性。burgdorferi 在蜱唾液和蜱肠提取物中孵育;以及（5）评估 潜在的使用蜱唾液蛋白，如I。肩突 抗补体蛋白（Isac），作为免疫原诱导保护性体液免疫， 以及对蜱虫取食和B的细胞免疫。伯氏传播 我们将尝试克隆那些编码特定蜱虫的基因 唾液蛋白或肽和唾液诱导的B。burgdorferi蛋白。 然后这些将在合适的质粒载体中表达。纯化 重组蛋白将用于各种疫苗接种方案中， 试图中和蜱抗补体活性在体外和 体内，并保护宿主免受疏螺旋体感染。因此，一个长 这项研究的范围目标是评估一种疫苗策略， 在病原体传播之前， 传输过程本身。另一个目标是评估新的B。 Burgdorferi蛋白作为潜在的疫苗候选物， 一旦病原体进入宿主体内就瞄准它最后是皂苷 佐剂QS-21将作为体液和细胞免疫刺激剂进行评价。 免疫力

Vector saliva appears to play a critical role in the successful bloodfeeding of hematophagous arthropods. Components of saliva serve to enhance pathogen transmission and host infection. Recent studies on the pharmacological properties of the saliva from Ixodes scapularis, the principal vector of Lyme disease spirochetes in the eastern U.S., reveal that its saliva contains substances that enhance bloodfeeding and perhaps determines vector competence. In particular, anticomplement activity in this tick's saliva may confer protection against complement-mediated killing of Borrelia burgdorferi and host rejection of the tick. In addition, saliva components modify protein expression in B. burgdorferi, perhaps enhancing infectivity of this bacterium, and certainly affecting the host response to infection. The proposed research will: (I) identify and characterize components of I. scapularis saliva responsible for anticomplement activity, and that affect protein expression in B. burgdorferi; (2) assess the protective effect of tick saliva fractions collected from various ixodid ticks (e.g. I. scapularis, Dermacentor variabilis, Amhlyomma americanum) on B. burgdorferi in a complement-based borreliacidal assay; (3) determine the effect of tick saliva on protein expression in B. burgdorferi and on the host immune response to infection; (4) evaluate the pathogenicity and invasiveness of B. burgdorferi incubated in tick saliva and tick gut extract; and (5) assess the potential of using tick salivary proteins, such as the I. scapularis anticomplement protein (Isac), as immunogens to induce protective humoral and cellular immunity to tick feeding and B. burgdorferi transmission. Attempts will be made to clone those genes encoding both specific tick salivary proteins or peptides and saliva-induced B. burgdorferi proteins. These will then be expressed in a suitable plasmid vector. Purified recombinant proteins will be used in various vaccination protocols in an attempt to neutralize the tick anticomplement activity in vitro and in vivo, and to protect the host against Borrelia infection. Thus, one long range goal of this research is to evaluate a vaccine strategy active against the tick vector prior to pathogen transmission and the transmission process itself. An additional goal is to evaluate new B. burgdorferi proteins as potential vaccine candidates that specifically target the pathogen upon entry into the host. Finally, the saponin adjuvant QS-21 will be evaluated as an stimulant of humoral and cellular immunity.