Erdile L F, Brandt M A, Warakomski D J, Westrack G J, Sadziene A, Barbour A G, Mays J P
Connaught Laboratories, Inc., Swiftwater, Pennsylvania 18370.
Infect Immun. 1993 Jan;61(1):81-90. doi: 10.1128/iai.61.1.81-90.1993.
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.
OspA是莱姆病螺旋体伯氏疏螺旋体的一种保护性抗原。全长伯氏疏螺旋体B31 OspA基因在大肠杆菌中的表达产生一种蛋白质，该蛋白质在翻译后由信号肽酶II进行加工，并含有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色谱法纯化。用OspA脂蛋白进行初次免疫和加强免疫，无论有无佐剂或吸附于明矾上，均可引发强烈的、剂量依赖性的免疫球蛋白G反应。接种疫苗小鼠的血清在体外可抑制螺旋体生长。用低至0.4微克OspA脂蛋白免疫两次的小鼠可抵抗10(4)个感染性螺旋体的皮内攻击。纯化的重组脂蛋白在无毒性佐剂的情况下诱导强烈保护反应的能力使其成为人类莱姆病疫苗的极佳候选抗原。相比之下，无论剂量如何，均未观察到对OspA非脂蛋白的血清免疫球蛋白G或生长抑制反应。OspA脂蛋白和非脂蛋白形式免疫原性的差异并非由于两种蛋白质抗原性的任何差异。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。
