Outer surface protein C (OspC), but not P39, is a protective immunogen against a tick-transmitted Borrelia burgdorferi challenge: Evidence for a conformational protective epitope in OspC

Outer surface protein C (OspC), but not P39, is a protective immunogen against a tick-transmitted Borrelia burgdorferi challenge: Evidence for a conformational protective epitope in OspC
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DOI:
10.1128/iai.64.6.2234-2239.1996
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发表时间:
1996-06-01
影响因子:
3.1
通讯作者:
Johnson, BJB
Johnson, BJB
中科院分区:
医学2区
文献类型:
--
作者:
Gilmore, RD;Kappel, KJ;Johnson, BJB

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用含有重组伯氏疏螺旋体B31(低传代)外表面蛋白C (OspC)或P39的大肠杆菌粗裂解物的可溶部分免疫远交系小鼠。血清转化后,通过蜱叮咬的自然传播方式给小鼠注射感染剂量的伯氏疏螺旋体B31。3只经P39免疫的小鼠无保护作用;经培养和血清学检测,12只重组ospc免疫小鼠均无感染。虽然OspC已被证明是一种保护性免疫原,可抵抗针注射体外培养的疏螺旋体的攻击,但本研究首次证明OspC对蜱传螺旋体的有效性。在进食后,所有蜱虫仍然携带伯氏螺旋体,这表明保护机制与蜱虫体内传染性螺旋体的破坏无关。在另一项实验中,用制备凝胶电泳纯化的伯氏疏螺旋体B31蛋白片段免疫4只小鼠,试图鉴定潜在的保护性抗原。许多小鼠对OspC产生了高滴度抗体反应,但奇怪的是,小鼠对通过蜱叮咬感染伯氏疏螺旋体很敏感。这些结果表明OspC上的保护性表位是热敏的/构象的,这一发现对疫苗开发具有重要意义。
Outbred mice were immunized with the soluble fraction of a crude Escherichia coli lysate containing either recombinant outer surface protein C (OspC) or P39 of Borrelia burgdorferi B31 (low passage). Following seroconversion, the mice were challenged with an infections dose of B. burgdorferi B31 via the natural transmission mode of tick bite. Three mice immunized with P39 were not protected; however, all 12 of the recombinant OspC-immunized mice were protected from infection as assayed by culture and serology. Although OspC has been shown to be a protective immunogen against challenge with in vitro-cultured borrelia administered by needle, this study is the first to demonstrate OspC effectiveness against tick-borne spirochetes. Following feeding, all ticks still harbored B. burgdorferi, suggesting that the mechanism of protection is not linked to destruction of the infectious spirochete within the tick. In a separate experiment, groups of four mice were immunized with protein fractions from B. burgdorferi B31 purified by preparative gel electrophoresis in an attempt to identify potential protective antigens. Many of these mice developed high-titer-antibody responses against OspC, but curiously the mice were susceptible to B. burgdorferi infection via tick bite. These results suggest that the protective epitope(s) on OspC is heat sensitive/conformational, a finding which has implications in vaccine development.