Probert W S, LeFebvre R B
Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California at Davis 95616.
Infect Immun. 1994 May;62(5):1920-6. doi: 10.1128/iai.62.5.1920-1926.1994.
Recent advances in the development of animal models for Lyme borreliosis have provided means of identifying potential targets for the design of a subunit vaccine to prevent this disease. The C3H/HeN mouse model was used to study several Borrelia burgdorferi antigens from a single isolate for their ability to elicit borreliacidal and protective antibodies. The ospA, ospB, ospC, ospD, and 83-kDa genes from a California isolate, SON 188, were cloned and expressed in Escherichia coli as proteins fused to the C-terminal end of maltose-binding protein. Active immunization of mice with these fusion proteins elicited high titers of antibodies that recognized the homologous SON 188 antigens upon immunoblotting. Antibodies generated to the OspA and OspB fusion proteins, but not to the OspC, OspD, and the 83-kDa fusion proteins, demonstrated in vitro borreliacidal activity. Challenge of all actively immunized mice with 10(7) SON 188 spirochetes resulted in infection in all mice receiving the OspD or 83-kDa immunogens but not in any mice receiving the OspA, OspB, or OspC fusion proteins. These results demonstrate the potential of OspA, OspB, and OspC as components of a subunit vaccine for the prevention of Lyme borreliosis.
莱姆病动物模型开发的最新进展为确定用于设计预防该疾病的亚单位疫苗的潜在靶点提供了方法。C3H/HeN小鼠模型被用于研究来自单一分离株的几种伯氏疏螺旋体抗原引发杀螺旋体抗体和保护性抗体的能力。来自加利福尼亚分离株SON 188的ospA、ospB、ospC、ospD和83-kDa基因被克隆，并在大肠杆菌中作为与麦芽糖结合蛋白C末端融合的蛋白质表达。用这些融合蛋白对小鼠进行主动免疫可引发高滴度抗体，这些抗体在免疫印迹时能识别同源SON 188抗原。针对OspA和OspB融合蛋白产生的抗体，而非针对OspC、OspD和83-kDa融合蛋白产生的抗体，表现出体外杀螺旋体活性。用10⁷个SON 188螺旋体对所有主动免疫的小鼠进行攻击，结果显示，接受OspD或83-kDa免疫原的所有小鼠均被感染，而接受OspA、OspB或OspC融合蛋白的小鼠均未感染。这些结果证明了OspA、OspB和OspC作为预防莱姆病亚单位疫苗成分的潜力。
