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Identification and characterization of Borrelia antigens as potential vaccine candidates against Lyme borreliosis.

机译:鉴定和鉴定作为抵抗莱姆病的潜在候选疫苗的鲍氏疏螺旋体抗原。

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The three Borrelia species, Borrelia afzelii, Borrelia burgdorferi and Borrelia garinii are the main species causing the most common tick-borne zoonosis, Lyme borreliosis. By applying a genomic approach relying on human antibodies we have identified 122 antigenic Borrelia proteins associated with Lyme borreliosis, including already known and published protective antigens. The heterogeneity of the Borrelia species causing Lyme borreliosis makes the search for conserved antigens providing broad protection challenging. Using several in vitro assays we narrowed down the selection to 15 vaccine candidates. These antigens were further analyzed for antigenicity and cross-reactivity using sera from mice infected with the three pathogenic Borrelia species. All antigens analyzed showed a high degree of cross-reactivity between the three Borrelia species, essential for providing cross-protection. We also investigated whether mice infected with B. afzelii through tick exposure are primed to mount cytokine responses. For a selection of these antigens, we observed preferentially a pro-inflammatory response in C3H/HeN mice, while in contrast also a type 2 T cell response was seen in the Borrelia-resistant mouse strain BALB/c. Thus, antigens mounting a type 2 or mixed type 2/type 1 T cell response might be preferred vaccine candidates for evaluation in animal models of Lyme borreliosis.Digital Object Identifier http://dx.doi.org/10.1016/j.vaccine.2011.10.073
机译:三种 Borrelia 物种 Borrelia afzelii , Borrelia burgdorferi 和 Borrelia garinii 是引起最常见壁虱的主要物种传播的人畜共患病,莱姆病。通过应用依赖人抗体的基因组方法,我们已经鉴定了122种与莱姆病(Lyme borreliosis)相关的抗原性博雷利亚蛋白(Borrelia ),包括已知的和公开的保护性抗原。导致莱姆病(Lyme borreliosis)的 Borrelia 菌种的异质性使得寻找提供广泛保护的保守抗原具有挑战性。使用几种体外分析,我们将选择范围缩小到15种候选疫苗。使用感染了三种致病性博雷利亚氏菌的小鼠血清进一步分析了这些抗原的抗原性和交叉反应性。分析的所有抗原均显示出三种种之间的高度交叉反应性,这对提供交叉保护至关重要。我们还调查了小鼠是否感染了iB。 afzelii通过tick暴露而引发细胞因子反应。对于这些抗原的选择,我们优先观察到了C3H / HeN小鼠的促炎反应,而与此相反,在耐鲍瑞里亚(Borrelia)的小鼠品系BALB / c中也观察到了2型T细胞反应。因此,携带2型或2型/ 1型混合T细胞反应的抗原可能是在莱姆病(Lyme borreliosis)动物模型中评估的首选候选疫苗。数字对象标识符http://dx.doi.org/10.1016/j.vaccine。 2011.10.073

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