Gipson Clay L, Davis Nancy L, Johnston Robert E, de Silva Aravinda M
Department of Microbiology and Immunology, University of North Carolina, CB# 7290, Chapel Hill, NC 27599, USA.
Vaccine. 2003 Sep 8;21(25-26):3875-84. doi: 10.1016/s0264-410x(03)00307-4.
Venezuelan Equine Encephalitis (VEE) virus replicon particles (VRPs) encoding Borrelia burgdorferi Outer surface protein A (OspA) were evaluated for their ability to induce an immune response and provide protection from tick-borne spirochetes. VRPs expressing ospA that accumulated intracellularly (VRP OspA) or that was secreted from host cells (VRP tPA-OspA) were tested. Both VRP OspA and VRP tPA-OspA expressed ospA in immunized mice. Mice vaccinated with VRPs expressing secreted OspA produced significant amounts of anti-OspA antibodies, whereas VRPs expressing intracellular OspA were less immunogenic. The VRP method of delivery induced a Th1 type immune response unlike the recombinant OspA protein in Freund's adjuvant, which induced a mixed (Th1 and Th2) immune response. The VRP tPA-OspA construct induced an immune response that reduced the bacterial load in feeding Ixodes scapularis and blocked transmission to the host. These results indicate that VRPs are capable of providing protection against tick-borne B. burgdorferi, and potentially can be used for developing improved vaccines against Lyme disease.
对编码伯氏疏螺旋体外表面蛋白A（OspA）的委内瑞拉马脑炎（VEE）病毒复制子颗粒（VRP）诱导免疫反应以及预防蜱传螺旋体感染的能力进行了评估。测试了表达在细胞内积累的ospA的VRP（VRP OspA）以及从宿主细胞分泌的VRP（VRP tPA - OspA）。VRP OspA和VRP tPA - OspA在免疫小鼠中均表达ospA。接种表达分泌型OspA的VRP的小鼠产生了大量抗OspA抗体，而表达细胞内OspA的VRP免疫原性较低。与弗氏佐剂中的重组OspA蛋白诱导混合（Th1和Th2）免疫反应不同，VRP递送方法诱导了Th1型免疫反应。VRP tPA - OspA构建体诱导的免疫反应降低了进食的肩突硬蜱中的细菌载量，并阻断了向宿主的传播。这些结果表明，VRP能够预防蜱传伯氏疏螺旋体感染，并且有可能用于开发改进的莱姆病疫苗。
