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首页> 外文期刊>Infection and immunity >Immunization with a Polyprotein Vaccine Consisting of the T-Cell Antigens Thiol-Specific Antioxidant, Leishmania major Stress-Inducible Protein 1, and Leishmania Elongation Initiation Factor Protects against Leishmaniasis
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Immunization with a Polyprotein Vaccine Consisting of the T-Cell Antigens Thiol-Specific Antioxidant, Leishmania major Stress-Inducible Protein 1, and Leishmania Elongation Initiation Factor Protects against Leishmaniasis

机译：用T细胞抗原硫醇特异性抗氧化剂，利什曼原虫主要应激诱导蛋白1和利什曼原虫延伸起始因子组成的多蛋白疫苗免疫预防利什曼原虫病。

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Development of an effective vaccine against Leishmania infection is a priority of tropical disease research. We have recently demonstrated protection against Leishmania major in the murine and nonhuman primate models with individual or combinations of purified leishmanial recombinant antigens delivered as plasmid DNA constructs or formulated with recombinant interleukin-12 (IL-12) as adjuvant. In the present study, we immunized BALB/c mice with a recombinant polyprotein comprising a tandem fusion of the leishmanial antigens thiol-specific antioxidant, L. major stress-inducible protein 1 (LmSTI1), and Leishmania elongation initiation factor (LeIF) delivered with adjuvants suitable for human use. Aspects of the safety, immunogenicity, and vaccine efficacy of formulations with each individual component, as well as the polyprotein referred to as Leish-111f, were assessed by using the L. major challenge model with BALB/c mice. No adverse reactions were observed when three subcutaneous injections of the Leish-111f polyprotein formulated with either MPL-squalene (SE) or Ribi 529-SE were given to BALB/c mice. A predominant Th1 immune response characterized by in vitro lymphocyte proliferation, gamma interferon production, and immunoglobulin G2A antibodies was observed with little, if any, IL-4. Moreover, Leish-111f formulated with MPL-SE conferred immunity to leishmaniasis for at least 3 months. These data demonstrate success at designing and developing a prophylactic leishmaniasis vaccine that proved effective in a preclinical model using multiple leishmanial antigens produced as a single protein delivered with a powerful Th1 adjuvant suitable for human use.
机译：开发针对利什曼原虫感染的有效疫苗是热带病研究的重点。我们最近在鼠类和非人灵长类动物模型中证明了针对个别 Leishmania major 的保护作用，它们以质粒DNA构建体的形式或以重组白介素12（IL-12）作为佐剂配制的纯化的利什曼重组抗原的个体或组合。在本研究中，我们用重组多蛋白免疫BALB / c小鼠，该蛋白包含利什曼原虫抗原硫醇特异性抗氧化剂 L的串联融合体。主要应激诱导蛋白1（LmSTI1）和利什曼原虫延伸起始因子（LeIF）随适合人类使用的佐剂一起递送。通过使用 L评估了具有每种单独成分的制剂以及称为Leish-111f的多蛋白的安全性，免疫原性和疫苗效力的方面。 BALB / c小鼠的主要攻击模型。当对BALB / c小鼠皮下注射用MPL-角鲨烯（SE）或Ribi 529-SE配制的Leish-111f多蛋白时，没有观察到不良反应。观察到以体外淋巴细胞增殖，γ干扰素产生和免疫球蛋白G2A抗体为特征的主要Th1免疫反应，几乎没有IL-4。此外，配制有MPL-SE的Leish-111f赋予至少3个月的利什曼病免疫力。这些数据证明了在设计和开发预防性利什曼病疫苗方面的成功，该疫苗在临床前模型中被证明是有效的，该疫苗使用多种利什曼病抗原作为单一蛋白生产，并与适用于人类的强大Th1佐剂一起递送。

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