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首页> 外文期刊>Infection and immunity >Protective vaccination with promastigote surface antigen 2 from Leishmania major is mediated by a TH1 type of immune response.
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Protective vaccination with promastigote surface antigen 2 from Leishmania major is mediated by a TH1 type of immune response.

机译：TH1型免疫应答介导了来自大利什曼原虫的前鞭毛体表面抗原2的保护性疫苗接种。

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Leishmania major promastigote surface antigen-2 complex (PSA-2) comprises a family of three similar but distinct polypeptides. The three PSA-2 polypeptides were purified from cultured promastigotes by a combination of detergent phase separation and monoclonal antibody affinity chromatography. Intraperitoneal vaccination of C3H/He mice with PSA-2 with Corynebacterium parvum as an adjuvant resulted in complete protection from lesion development after challenge infection with virulent L. major. Significant protection was also obtained in the genetically susceptible BALB/cH-2k and BALB/c mice. One of the PSA-2 genes was cloned and expressed in both Escherichia coli and Leishmania mexicana promastigotes. Vaccination with the recombinant PSA-2 purified from E. coli did not confer protection, in contrast to the L. mexicana-derived recombinant PSA-2, which provided excellent protection. CD4+ T cells isolated from the spleens of vaccinated mice produced large amounts of gamma interferon but no detectable interleukin 4 upon stimulation with PSA-2 in vitro. Limiting dilution analysis showed a marked increase in the precursor frequency of PSA-2-specific gamma interferon-secreting CD4+ T cells. No substantial change in precursor frequency was observed for interleukin 4-secreting T cells in the vaccinated mice. A CD4+ PSA-2 specific T-cell line generated from splenocytes of a vaccinated mouse produces a cytokine pattern consistent with a TH1 phenotype. Intravenous injection of this line into naive mice reduced significantly the parasite burden upon challenge infection. Taken together, the data suggest that vaccination with PSA-2 induces a TH1 type of immune response which protects mice from L. major infection. Moreover, a single recombinant PSA-2 polypeptide derived from a genomic clone can also vaccinate, provided that the structural form of the antigen is near native.
机译：利什曼原虫主要前鞭毛体表面抗原2复合物（PSA-2）包含三个相似但截然不同的多肽家族。通过去污剂相分离和单克隆抗体亲和层析相结合，从培养的前鞭毛体中纯化出三种PSA-2多肽。用强力棒杆菌攻击感染后，用小棒状杆菌作为佐剂用PSA-2对C3H / He小鼠进行腹膜内疫苗接种，可完全保护其免受病变的侵害。在遗传易感的BALB / cH-2k和BALB / c小鼠中也获得了重要的保护。 PSA-2基因之一被克隆并在大肠杆菌和墨西哥利什曼原虫前鞭毛体中表达。与源自墨西哥乳杆菌的重组PSA-2提供了优异的保护相比，用从大肠杆菌纯化的重组PSA-2进行的疫苗接种没有提供保护。从接种小鼠的脾脏分离的CD4 + T细胞在体外用PSA-2刺激后产生大量的γ干扰素，但未检测到白介素4。极限稀释分析显示PSA-2特异性分泌γ干扰素的CD4 + T细胞的前体频率显着增加。在接种的小鼠中，对于分泌白介素4的T细胞，未观察到前体频率的实质性变化。从接种小鼠的脾细胞产生的CD4 + PSA-2特异性T细胞系产生与TH1表型一致的细胞因子模式。向幼稚小鼠静脉内注射该品系显着降低了激发感染后的寄生虫负担。两者合计，数据表明用PSA-2疫苗接种可诱导TH1类型的免疫反应，从而保护小鼠免受大肠埃希氏菌感染。此外，只要抗原的结构形式接近天然，衍生自基因组克隆的单个重组PSA-2多肽也可以接种。

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