TICK SALIVA AND LYME DISEASE AND VACCINE STRATEGY

媒介唾液似乎在成功的 食血节肢动物的食血行为。唾液的成分用来 加强病原体传播和宿主感染。近几年来的研究进展 肩部硬蜱唾液药理性质的研究 莱姆病螺旋体在美国东部的主要媒介，揭示 它的唾液含有促进血液摄取的物质，也许 决定了媒介的能力。特别是，体内的抗补体活性 这种扁虱的唾液可能会提供对补体介导的保护 伯氏疏螺旋体的杀灭和宿主对扁虱的排斥。在……里面 此外，唾液成分改变了伯氏杆菌的蛋白质表达， 可能会增强这种细菌的传染性，当然也会影响 宿主对感染的反应。拟议的研究将：(I)确定 并鉴定了肩周炎唾液中负责 抗补体活性，并影响B。 (2)评价扁虱唾液组分的保护作用 收集自各种硬蜱(例如：肩部硬蜱、革蜱) 可变变种(Amhlyomma Americanum)对伯氏杆菌的影响 杀灭螺旋体试验；(3)测定壁虱唾液对蛋白质的影响 在伯氏杆菌中的表达和宿主对感染的免疫反应； (4)评价伯氏杆菌的致病性和侵袭性。 在壁虱唾液和壁虱肠道提取液中孵化；以及(5)评估 利用扁虱唾液蛋白的可能性，如我的肩周炎 抗补体蛋白(ISAc)作为免疫原诱导保护性体液 以及对扁虱摄食和伯氏杆菌传播的细胞免疫力。 将尝试克隆编码这两种特定扁虱的基因 唾液蛋白或多肽以及唾液诱导的伯氏杆菌蛋白。 然后，这些基因将在合适的质粒载体中表达。纯净的 重组蛋白将用于不同的疫苗接种方案 在体外和体内中和扁虱抗补体活性的尝试 活体，并保护宿主免受疏螺旋体感染。因此，一个长的 这项研究的范围目标是评估一种有效的疫苗策略 在病原体传播之前对扁虱媒介和 传播过程本身。另一个目标是评估新的B。 Burgdorferi蛋白作为潜在的候选疫苗， 当病原体进入宿主时，将其作为靶标。最后，皂素 佐剂QS-21将被评价为体液和细胞刺激剂 豁免权。

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.