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Role of attached lipid in immunogenicity of Borrelia burgdorferi OspA.

机译:附着脂质在伯氏疏螺旋体OspA免疫原性中的作用。

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OspA is a protective antigen of the Lyme disease spirochete Borrelia burgdorferi. Expression of the full-length B. burgdorferi B31 OspA gene in Escherichia coli produces a protein that is processed posttranslationally by signal peptidase II and contains an attached lipid moiety. The recombinant OspA lipoprotein has been purified by detergent extraction and ion-exchange chromatography. Priming and boosting with OspA lipoprotein, either with no adjuvant or adsorbed to alum, elicited a strong, dose-dependent immunoglobulin G response. Serum from vaccinated mice inhibited spirochetal growth in vitro. Mice immunized twice with as little as 0.4 micrograms of OspA lipoprotein were protected against an intradermal challenge with 10(4) infectious spirochetes. The ability of the purified recombinant lipoprotein to induce a strong protective response in the absence of toxic adjuvants makes it an excellent candidate antigen for a human vaccine against Lyme disease. By contrast, no serum immunoglobulin G or growth inhibitory response to OspA nonlipoprotein was seen at any dose. The difference in immunogenicities of the lipoprotein and nonlipoprotein forms of OspA is not due to any difference in the antigenicities of the two proteins. These results suggest that posttranslational lipid attachment is a critical determinant of the immunogenicity of the OspA protein.
机译:OspA是莱姆病螺旋体疏螺旋体伯氏疏螺旋体的保护性抗原。全长B. burgdorferi B31 OspA基因在大肠杆菌中的表达产生一种蛋白质,该蛋白质通过信号肽酶II进行翻译后加工,并包含一个附着的脂质部分。重组OspA脂蛋白已通过去污剂提取和离子交换层析纯化。没有佐剂或不吸附到明矾上的OspA脂蛋白引发和加强免疫,会引起强烈的剂量依赖性免疫球蛋白G反应。接种小鼠的血清在体外抑制螺旋体生长。用低至0.4微克的OspA脂蛋白免疫两次的小鼠可通过10(4)感染性螺旋体保护免受皮内攻击。在没有毒性佐剂的情况下,纯化的重组脂蛋白诱导强烈保护反应的能力使其成为抗莱姆病人疫苗的极佳候选抗原。相反,在任何剂量下均未观察到血清免疫球蛋白G或对OspA非脂蛋白的生长抑制反应。 OspA的脂蛋白和非脂蛋白形式的免疫原性差异不是由于两种蛋白的抗原性差异。这些结果表明,翻译后脂质附着是OspA蛋白免疫原性的关键决定因素。

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