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首页> 外文期刊>Infection and immunity >Immunity against Yersinia enterocolitica by vaccination with Yersinia HSP60 immunostimulating complexes or Yersinia HSP60 plus interleukin-12.
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Immunity against Yersinia enterocolitica by vaccination with Yersinia HSP60 immunostimulating complexes or Yersinia HSP60 plus interleukin-12.

机译：通过接种耶尔森氏菌HSP60免疫刺激复合物或耶尔森氏菌HSP60加白细胞介素12来免疫小肠结肠炎耶尔森菌。

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Microbial heat shock proteins (HSP) are dominant antigens for the host immune response. Because of the high sequence homology between mammalian and microbial HSP, their value as component of a subunit vaccine has been the subject of controversy. Previous work from this laboratory, however, demonstrated for the first time that the adoptive transfer of HSP60-reactive CD4+ alphabeta T-cell clones confers protection against bacterial infection in mice but does not induce autoimmunity. In the present study, we have therefore evaluated the potential role of Yersinia HSP60 (Y-HSP60) as a vaccine in the Yersinia enterocolitica mouse infection model. For this purpose, immunostimulating complexes (ISCOM) which included Y-HSP60 were constructed. Parenteral administration of this vaccine induced high Y-HSP60-specific serum antibody responses as well as T-cell responses. This reaction was parallelled by immunity against a lethal challenge with Y. enterocolitica. In contrast, mucosal application of Y-HSP60-ISCOM failed to induce systemic Y-HSP60-specific T-cell responses and thus failed to induce immunity against yersiniae. Likewise, vaccination with purified recombinant Y-HSP60 induced antibody responses but only weak T-cell responses. Therefore, this vaccination protocol was not protective. However, when interleukin-12 was used as an adjuvant, purified Y-HSP60 induced significant Y-HSP60-specific T-cell responses and thus induced protection against subsequent challenge with yersiniae. These studies suggest that (i) microbial HSP might be promising candidates for the design of subunit vaccines and (ii) interleukin-12 is an efficient alternative adjuvant to ISCOM particles for induction of protective CD4 Th1-cell-dependent immune responses against bacterial pathogens.
机译：微生物热激蛋白（HSP）是宿主免疫反应的主要抗原。由于哺乳动物和微生物HSP之间的高度同源性，它们作为亚单位疫苗成分的价值一直是争议的主题。但是，该实验室的先前工作首次证明了HSP60反应性CD4 +字母T细胞克隆的过继转移可赋予小鼠抗细菌感染的保护能力，但不会诱导自身免疫。因此，在本研究中，我们评估了耶尔森氏菌HSP60（Y-HSP60）作为疫苗在小肠结肠炎耶尔森菌小鼠感染模型中的潜在作用。为此，构建了包括Y-HSP60的免疫刺激复合物（ISCOM）。该疫苗的肠胃外给药引起高的Y-HSP60特异性血清抗体应答以及T细胞应答。通过抵抗小肠结肠炎耶尔森氏菌的致死性免疫力使该反应平行。相反，Y-HSP60-ISCOM的粘膜应用未能诱导全身性Y-HSP60特异性T细胞反应，因此未能诱导针对耶尔森氏菌的免疫力。同样，用纯化的重组Y-HSP60疫苗接种可诱导抗体反应，但仅产生弱T细胞反应。因此，该疫苗接种方案不是保护性的。但是，当白介素12用作佐剂时，纯化的Y-HSP60诱导明显的Y-HSP60特异性T细胞应答，从而诱导针对耶尔森氏菌的后续攻击的保护作用。这些研究表明（i）微生物HSP可能是设计亚单位疫苗的有前途的候选者，并且（ii）白介素12是ISCOM颗粒的有效替代佐剂，用于诱导针对细菌病原体的保护性CD4 Th1细胞依赖性免疫应答。

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