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首页> 外文期刊>Parasitology >Peripheral expression of LACK-mRNA induced by intranasal vaccination with PCI-NEO-LACK defines the protection duration against murine visceral leishmaniasis
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Peripheral expression of LACK-mRNA induced by intranasal vaccination with PCI-NEO-LACK defines the protection duration against murine visceral leishmaniasis

机译：通过PCI-NEO-LACK鼻内疫苗接种诱导的LACK-mRNA的外周表达定义了针对鼠内脏利什曼病的保护期

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摘要

LACK (Leishmania analogue of the receptor kinase C) is a conserved protein in the protozoan of the genus Leishmania, which is associated with the immunopathogenesis and susceptibility of BALB/c mice to Leishmania major infection. We previously demonstrated that intranasal immunization with a plasmid DNA encoding the p36/LACK leishmanial antigen (pCI-neo-LACK) followed by challenge 7 days after a booster dose effectively protects BALB/c mice against both cutaneous and visceral leishmaniasis. In the present study, the correlation between systemic mRNA expression after nasal DNA uptake, and the duration of protective immunity was addressed. LACK mRNA transcripts were detected in the spleen, brain, cervical lymph nodes and popliteal lymph nodes as early as 7 days, lasting 3 months after vaccination with pCI-neo-LACK. The kinetics of transcript expression correlated with enhanced cutaneous hypersensitivity against parasite antigens. Leishmania chagasi infection at 7 days or 3 months, but not 6 months after vaccination resulted in significantly lower parasite loads as compared with non-vaccinated controls. Protection also correlated with enhanced spleen cell responsiveness to parasite antigens leading to increased IFN- ? and IL-4 and decreased IL-10 production. Together, these data demonstrate that the protection conferred by the intranasal DNA vaccine lasts at least 3 months and is associated with expression of vaccine mRNA in peripheral organs.
机译：LACK（受体激酶C的利什曼原虫类似物）是利什曼原虫属原生动物中的保守蛋白，与BALB / c小鼠对利什曼原虫的严重感染具有免疫原性和敏感性。我们先前证明，鼻内免疫接种的编码p36 / LACK利什曼原虫抗原（pCI-neo-LACK）的质粒DNA，在加强剂量后7天进行攻击，可以有效地保护BALB / c小鼠免受皮肤和内脏利什曼病的侵害。在本研究中，研究了鼻DNA摄取后全身mRNA表达与保护性免疫持续时间之间的相关性。接种pCI-neo-LACK后持续3个月，最早在第7天就在脾脏，脑，颈淋巴结和pop淋巴结中检测到LACK mRNA转录本。转录表达的动力学与增强的针对寄生虫抗原的皮肤超敏性相关。与未接种疫苗的对照组相比，接种疫苗后7天或3个月（但不是6个月）的利什曼原虫恰加斯病感染导致的寄生虫载量显着降低。保护作用还与脾细胞对寄生虫抗原的反应性增强有关，导致IFN-γ增加。 IL-4和降低的IL-10产量。总之，这些数据表明鼻内DNA疫苗赋予的保护至少持续3个月，并且与疫苗mRNA在外周器官中的表达有关。

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