Bockenstedt L K, Hodzic E, Feng S, Bourrel K W, de Silva A, Montgomery R R, Fikrig E, Radolf J D, Barthold S W
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8031, USA.
Infect Immun. 1997 Nov;65(11):4661-7. doi: 10.1128/iai.65.11.4661-4667.1997.
Antibodies to the outer surface proteins (Osps) A, B, and C of the spirochete Borrelia burgdorferi can prevent infection in animal models of Lyme borreliosis. We have previously demonstrated that immune serum from mice infected with B. burgdorferi N40 can also prevent challenge infection and induce disease regression in infected mice. The antigens targeted by protective and disease-modulating antibodies are presently unknown, but they do not include Osp A or Osp B. Because Osp C antibodies are present in immune mouse serum, we investigated the ability of hyperimmune serum to recombinant Osp C (N40) to protect mice against challenge infection with N40 spirochetes. In both active and passive immunization studies, Osp C (N40) antiserum failed to protect mice from challenge infection with cultured organisms. Mice actively immunized with recombinant Osp C (N40) were susceptible to tick-borne challenge infection, and nymphal ticks remained infected after feeding on Osp C-hyperimmunized mice. In contrast, similar immunization studies performed with Osp C (PKo) antiserum prevented challenge infection of mice with a clone of PKo spirochetes pathogenic for mice. Both Osp C (N40) and Osp C (PKo) antisera showed minimal in vitro borreliacidal activity, and immunofluorescence studies localized Osp C beneath the outer membrane of both N40 and PKo spirochetes. We conclude that Osp C antibody-mediated immunity is strain specific and propose that differences in Osp C surface expression by spirochetes in vivo may account for strain-specific immunity.
抗疏螺旋体伯氏疏螺旋体外表面蛋白(Osp)A、B和C的抗体可在莱姆病疏螺旋体病的动物模型中预防感染。我们之前已证明,感染伯氏疏螺旋体N40的小鼠的免疫血清也能预防激发感染,并促使感染小鼠的疾病消退。目前尚不清楚保护性抗体和调节疾病的抗体所靶向的抗原,但它们不包括Osp A或Osp B。由于免疫小鼠血清中存在Osp C抗体,我们研究了重组Osp C(N40)的超免疫血清保护小鼠免受N40螺旋体激发感染的能力。在主动免疫和被动免疫研究中,Osp C(N40)抗血清均未能保护小鼠免受培养的病原体的激发感染。用重组Osp C(N40)进行主动免疫的小鼠易受蜱传播的激发感染,若虫蜱在吸食Osp C超免疫小鼠后仍被感染。相比之下,用Osp C(PKo)抗血清进行的类似免疫研究可预防小鼠受到对小鼠致病的PKo螺旋体克隆的激发感染。Osp C(N40)和Osp C(PKo)抗血清在体外均显示出最小的杀疏螺旋体活性,免疫荧光研究将Osp C定位在N40和PKo螺旋体的外膜下方。我们得出结论,Osp C抗体介导的免疫具有菌株特异性,并提出螺旋体在体内Osp C表面表达的差异可能是菌株特异性免疫的原因。