Zhong W, Gern L, Stehle T, Museteanu C, Kramer M, Wallich R, Simon M M
Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
Eur J Immunol. 1999 Mar;29(3):946-57. doi: 10.1002/(SICI)1521-4141(199903)29:03<946::AID-IMMU946>3.0.CO;2-P.
Vaccination with outer surface protein A (OspA) of Borrelia burgdorferi prevents subsequent infection and disease in both laboratory animals and humans with high efficacy. OspA-based immunity, however, does not affect established infection due to the loss of OspA expression in the vertebrate host. We show here that repeated passive transfer of mouse and/or rabbit immune sera to recombinant GST-OspC fusion protein resulted in a dose-dependent resolution (1) of fully established arthritis and carditis as well as infection in needle-challenged C.B-17 SCID and (2) of infection in both experimentally and tick-infected BALB/c mice. Unexpectedly, active immunization of disease-susceptible AKR/N mice with GST-OspC only led to prevention but not resolution of disease and infection, in spite of high serum titers of OspC-specific Ab and the expression of ospC in tissue-derived spirochetes. The data suggest that the efficacy of OspC antibody-mediated immunity depends on the immunological history of the recipient and/or environment-dependent regulation of OspC surface expression by spirochetes in vivo. The results encourage further attempts to develop therapeutic vaccination protocols against Lyme disease.
用伯氏疏螺旋体的外表面蛋白A(OspA)进行疫苗接种,在实验室动物和人类中都能高效预防后续感染和疾病。然而,由于脊椎动物宿主中OspA表达的丧失,基于OspA的免疫并不影响已确立的感染。我们在此表明,将小鼠和/或兔免疫血清反复被动转移至重组GST - OspC融合蛋白,可导致(1)在针刺感染的C.B - 17 SCID小鼠中,已完全确立的关节炎、心肌炎以及感染呈剂量依赖性消退,以及(2)在实验性和蜱感染的BALB/c小鼠中感染消退。出乎意料的是,用GST - OspC对易感疾病的AKR/N小鼠进行主动免疫,尽管OspC特异性抗体的血清滴度很高且组织来源的螺旋体中ospC表达,但仅导致疾病和感染的预防而非消退。数据表明,OspC抗体介导的免疫效力取决于受体的免疫史和/或体内螺旋体对OspC表面表达的环境依赖性调节。这些结果鼓励进一步尝试开发针对莱姆病的治疗性疫苗接种方案。