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首页> 外文期刊>Infection and immunity >Protection against Intestinal Amebiasis by a Recombinant Vaccine Is Transferable by T Cells and Mediated by Gamma Interferon
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Protection against Intestinal Amebiasis by a Recombinant Vaccine Is Transferable by T Cells and Mediated by Gamma Interferon

机译：重组疫苗对肠道阿米巴病的保护可通过T细胞转移并由γ干扰素介导。

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We have previously shown that vaccination with purified Entamoeba histolytica Gal/GalNAc lectin or recombinant subunits can protect mice from intestinal amebiasis upon intracecal challenge. In this study, we demonstrated with adoptive-transfer experiments that this lectin vaccine protection is mediated by T cells but not serum. The cell-mediated immune (CMI) response was characterized by significant gamma interferon (IFN-γ), interleukin 12 (IL-12), IL-2, IL-10, and IL-17 production. To move toward a human vaccine, we switched to a recombinant protein and tested a range of adjuvants and routes appropriate for humans. We found that subcutaneous delivery of LecA with IDRI's adjuvant system EM014 elicited a potent Th1-type CMI profile and provided significant protection, as measured by culture negativity (79% efficacy); intranasal immunization with cholera toxin provided 56% efficacy; and alum induced a Th2-type response that protected 62 to 68% of mice. Several antibody and CMI cytokine responses were examined for correlates of protection, and prechallenge IFN-γ+ or IFN-γ-, IL-2-, and tumor necrosis factor alpha-triple-positive CD4 cells in blood were statistically associated with protection. To test the role of IFN-γ in LecA-mediated protection, we neutralized IFN-γ in LecA-immunized mice and found that it abrogated the protection conferred by vaccination. These data demonstrate that CMI is sufficient for vaccine protection from intestinal amebiasis and reveal an important role for IFN-γ, even in the setting of alum.
机译：先前我们已经证明，用纯化的溶组织阿米巴 Gal / GalNAc凝集素或重组亚基进行疫苗接种可以保护小鼠免受内源性挑战引起的肠道阿米巴病。在这项研究中，我们通过过继转移实验证明了这种凝集素疫苗的保护作用是由T细胞而非血清介导的。细胞介导的免疫（CMI）反应的特征在于明显的γ干扰素（IFN-γ），白介素12（IL-12），IL-2，IL-10和IL-17的产生。为了开发人类疫苗，我们改用了重组蛋白，并测试了一系列适合人类的佐剂和途径。我们发现，通过IDRI辅助系统EM014皮下递送LecA可以产生有效的Th1型CMI谱，并提供了显着的保护作用（通过培养阴性率来衡量）（79％的功效）;霍乱毒素鼻内免疫提供了56％的功效;和明矾诱导的Th2型反应可保护62％至68％的小鼠。检查了几种抗体和CMI细胞因子反应的保护相关性，以及血中挑战前的IFN-γ + 或IFN-γ-，IL-2-和肿瘤坏死因子α-三联体阳性CD4细胞在统计学上与保护相关。为了测试IFN-γ在LecA介导的保护中的作用，我们中和了LecA免疫小鼠中的IFN-γ，发现它取消了疫苗接种所赋予的保护作用。这些数据表明，CMI足以保护疫苗免受肠道阿米巴病的侵害，甚至在明矾环境中也显示出IFN-γ的重要作用。

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