Barthold S W, Fikrig E, Bockenstedt L K, Persing D H
Section of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Infect Immun. 1995 Jun;63(6):2255-61. doi: 10.1128/iai.63.6.2255-2261.1995.
Outer surface protein A (OspA), which is abundantly expressed in cultured Borrelia burgdorferi, appears to be down-regulated or masked following low-dose infection, and OspA immunization did not prevent infection, dissemination, or disease development with host-adapted spirochetes. Seroconversion of mice to B. burgdorferi OspA depended on dose and viability of inoculated spirochetes. Mice inoculated with > 10(4) live spirochetes and > 10(7) heat-killed spirochetes seroconverted to OspA, but mice inoculated with fewer spirochetes did not seroconvert to OspA at 2 weeks after inoculation. Growth temperature of spirochetes was not a factor for infectious dose or seroconversion to OspA. Spirochetes grown at 30, 34, or 38 degrees C had the same median infectious dose. Growth temperature did not influence infectious dose when mice were inoculated intraperitoneally or intradermally and did not influence dose-related immunologic recognition of OspA. Mice hyperimmunized with recombinant OspA-glutathione S-transferase (GT) fusion protein or GT (controls) were challenged by syringe inoculation with 10(3) spirochetes or by transplantation of infected skin from syngenic mice infected for 2 or 8 weeks. OspA-GT-immunized mice resisted syringe challenge but developed disseminated infections following transplantation of infected skin. Identical results were obtained in mice passively immunized with hyperimmune serum to OspA-GT or GT and then challenged by syringe or infected skin transplant. The number of spirochetes in infected skin, determined by quantitative PCR directed toward both plasmid and genomic targets, was less than the syringe challenge dose.
外表面蛋白A(OspA)在培养的伯氏疏螺旋体中大量表达,但在低剂量感染后似乎会下调或被掩盖,并且OspA免疫并不能预防宿主适应性螺旋体的感染、播散或疾病发展。小鼠对伯氏疏螺旋体OspA的血清转化取决于接种螺旋体的剂量和活力。接种>10⁴活螺旋体和>10⁷热灭活螺旋体的小鼠血清转化为OspA,但接种较少螺旋体的小鼠在接种后2周未血清转化为OspA。螺旋体的生长温度不是感染剂量或血清转化为OspA的影响因素。在30、34或38℃下生长的螺旋体具有相同的半数感染剂量。当小鼠通过腹腔内或皮内接种时,生长温度不影响感染剂量,也不影响与剂量相关的OspA免疫识别。用重组OspA-谷胱甘肽S-转移酶(GT)融合蛋白或GT(对照)进行超免疫的小鼠,通过注射器接种10³螺旋体或移植来自感染2周或8周的同基因小鼠的感染皮肤进行攻击。用OspA-GT免疫的小鼠抵抗注射器攻击,但在移植感染皮肤后发生播散性感染。在用针对OspA-GT或GT的超免疫血清被动免疫然后通过注射器攻击或感染皮肤移植进行攻击的小鼠中获得了相同的结果。通过针对质粒和基因组靶点的定量PCR确定,感染皮肤中的螺旋体数量少于注射器攻击剂量。