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首页> 外文期刊>Infection and immunity >VraA (BBI16) Protein of Borrelia burgdorferi Is a Surface-Exposed Antigen with a Repetitive Motif That Confers Partial Protection against Experimental Lyme Borreliosis
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VraA (BBI16) Protein of Borrelia burgdorferi Is a Surface-Exposed Antigen with a Repetitive Motif That Confers Partial Protection against Experimental Lyme Borreliosis

机译：伯氏疏螺旋体的VraA（BBI16）蛋白是一种表面暴露的抗原，具有重复性基序，可部分保护实验性莱姆疏螺旋体病

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We have previously described the expression cloning of nineBorrelia burgdorferi antigens, using rabbit serum enriched for antibodies specific for infection-associated antigens, and determined that seven of these antigens were associated with infectiousB. burgdorferi strain B31. One of these infection-associated antigens encoded a 451-amino-acid putative lipoprotein containing 21 consecutive and invariant 9-amino-acid repeat sequences near the amino terminus that we have designated VraA for virulent strain-associated repetitive antigen A. The vraAlocus (designated BBI16 by The Institute for Genomic Research) maps to one of the 28-kb linear plasmids (designated lp28-4) that is not present in noninfectious strain B31 isolates. Subsequent PCR analysis of clonal isolates of B. burgdorferi B31 from infected mouse skin revealed a clone that lacked only lp28-4. Southern blot and Western blot analyses indicated that the lp28-4 and VraA proteins, respectively, were missing from this clone. We have also determined that VraA is a surface-exposed protein based on protease accessibility assays of intact whole cells. Furthermore, vraA expression is modestly derepressed when cells are grown at 37°C relative to cells grown at 32°C, suggesting that VraA is, in part, a temperature-inducible antigen. Homologues cross-reactive to B. burgdorferi B31 VraA, most with different molecular masses, were identified in several B. burgdorferi sensu lato isolates, including B. andersonii, suggesting that the immunogenic epitope(s) present in strain B31 VraA is conserved betweenBorrelia spp. In protection studies, only 8.3% of mice (1 of 12) immunized with full-length recombinant VraA fused to glutathioneS-transferase (GST) were susceptible to infectious challenge with 102 B. burgdorferi strain B31, whereas naive mice or mice immunized with GST alone were infected 40% or 63 to 67% (depending on tissues assayed) of the time, respectively. As such, the partial protection elicited by VraA immunization provides an additional testable vaccine candidate to help protect against Lyme borreliosis.
机译：我们先前已经描述了使用富集了感染相关抗原特异性抗体的兔血清对九种伯氏疏螺旋体抗原的表达克隆，并确定这些抗原中有七种与传染性B抗原相关。 burgdorferi菌株B31。这些与感染相关的抗原之一编码一个451个氨基酸的推定脂蛋白，该蛋白在氨基末端附近包含21个连续且不变的9个氨基酸重复序列，我们将VraA指定为毒力相关的重复性抗原A。 vraA基因座（由基因组研究所指定为BBI16）映射到28 kb线性质粒之一（命名为lp28-4），该质粒在非感染性B31分离株中不存在。随后对 B的克隆分离物进行PCR分析。感染的小鼠皮肤中的burgdorferi B31揭示了一个仅缺少lp28-4的克隆。 Southern印迹和Western印迹分析表明，该克隆分别缺少lp28-4和VraA蛋白。我们还基于完整完整细胞的蛋白酶可及性分析确定了VraA是一种表面暴露的蛋白质。此外，相对于32°C的细胞，在37°C的细胞生长时， vraA 的表达会适度降低，这表明VraA在某种程度上是一种温度诱导性抗原。同源物与 B交叉反应。在几个 B中鉴定出burgdorferi B31 VraA，大多数具有不同的分子质量。 burgdorferi sensu lato分离株，包括 B。 Andersonii ，表明B31 VraA株中存在的免疫原性表位在 Borrelia spp之间是保守的。在保护研究中，只有8.3％（12只中的1只）的小鼠接受了与谷胱甘肽 S -转移酶（GST）融合的全长重组VraA免疫，受到10 2 B。 burgdorferi菌株B31，而未感染的小鼠或仅用GST免疫的小鼠则分别感染40％或63％至67％（取决于所检测的组织）。这样，通过VraA免疫引起的部分保护提供了另一种可测试的疫苗候选物，以帮助预防莱姆病。

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