Fukumoto Shinya, Xuan Xuenan, Kadota Kimie, Igarashi Ikuo, Sugimoto Chihiro, Fujisaki Kozo, Nagasawa Hideyuki, Mikami Takeshi, Suzuki Hiroshi
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan.
Clin Diagn Lab Immunol. 2003 Jul;10(4):596-601. doi: 10.1128/cdli.10.4.596-601.2003.
Previously, we identified an immunodominant antigen, P50 of Babesia gibsoni. In the present study, the gene encoding the truncated P50 (rP50t) without a C-terminal hydrophobic region (29 amino acids [aa]) was expressed in insect cells by a recombinant baculovirus. The highly hydrophobic C-terminal 20-aa regions seems to be a transmembrane region, which was evidenced by the fact that rP50t was effectively secreted into the supernatant of insect cells infected with the recombinant baculovirus. N-terminal amino acid sequence analysis of rP50t indicated that N-terminal 19 aa function as a signal peptide. The expression level of rP50t reached up to 2 mg per 10(8) cells infected with the recombinant baculovirus. The immunogenic property of rP50t was evaluated by an immunization test in mice. Mice immunized with rP50t induced a high-level antibody titer against the B. gibsoni merozoite. Monoclonal antibodies (MAbs) to rP50t were produced in mice to determine the immunogenic regions of P50. The epitope(s) recognized by all five MAbs were located between aa 190 and 273, suggesting that the central part of P50 is a highly immunogenic region. The diagnostic potential of rP50t was evaluated using an enzyme-linked immunosorbent assay (ELISA). The ELISA was able to differentiate clearly (P < 0.0001) between B. gibsoni-infected dog serum and B. canis-infected dog serum or noninfected dog serum. Our results indicated that the rP50t may provide a useful potential immunogenic reagent for use in diagnosis and as a subunit vaccine to control B. gibsoni infection in dogs.
此前,我们鉴定出了吉氏巴贝斯虫的一种免疫显性抗原P50。在本研究中,编码不含C端疏水区域(29个氨基酸[aa])的截短型P50(rP50t)的基因通过重组杆状病毒在昆虫细胞中表达。高度疏水的C端20个氨基酸区域似乎是一个跨膜区域,这一点可由rP50t有效分泌到感染重组杆状病毒的昆虫细胞上清液中得到证明。对rP50t的N端氨基酸序列分析表明,N端19个氨基酸起信号肽的作用。rP50t的表达水平在感染重组杆状病毒的每10⁸个细胞中可达2毫克。通过在小鼠中进行免疫试验评估了rP50t的免疫原性。用rP50t免疫的小鼠诱导出了针对吉氏巴贝斯虫子孢子的高水平抗体滴度。在小鼠中制备了针对rP50t的单克隆抗体(MAbs),以确定P50的免疫原性区域。所有五种MAbs识别的表位位于氨基酸190至273之间,这表明P50的中部是一个高度免疫原性区域。使用酶联免疫吸附测定(ELISA)评估了rP50t的诊断潜力。该ELISA能够清晰地区分(P < 0.0001)感染吉氏巴贝斯虫的犬血清与感染犬巴贝斯虫的犬血清或未感染犬血清。我们的结果表明,rP50t可能为犬类吉氏巴贝斯虫感染的诊断和作为亚单位疫苗提供一种有用的潜在免疫原性试剂。