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MVA-LACK as a safe and efficient vector for vaccination against leishmaniasis.

机译：MVA-LACK是用于接种抗利什曼病的安全有效载体。

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摘要

An optimal vaccine against leishmaniasis should elicit parasite specific CD4+ and cytotoxic CD8+ T cells. In this investigation, we described a prime/boost immunization approach based on DNA and on poxvirus vectors (Western Reserve, WR, and the highly attenuated modified vaccinia virus Ankara, MVA), both expressing the LACK antigen of Leishmania infantum, that triggers different levels of specific CD8+ T cell responses and protection (reduction in lesion size and parasitemia) against L. major infection in mice. A prime/boost vaccination with DNA-LACK/MVA-LACK elicits higher CD8+ T cell responses than a similar protocol with the replication competent VV-LACK. Both CD4+ and CD8+ T cells were induced by DNA-LACK/MVA-LACK immunization. The levels of IFN-gamma and TNF-alpha secreting CD8+ T cells were higher in splenocytes from DNA-LACK/MVA-LACK than in DNA-LACK/VV-LACK immunized animals. Moreover, protection against L. major was significantly higher in DNA-LACK/MVA-LACK than in DNA-LACK/VV-LACK immunized animals when boosted with the same virus dose, and correlated with high levels of IFN-gamma and TNF-alpha secreting CD8+ T cells. In DNA-LACK/MVA-LACK vaccinated animals, the extent of lesion size reduction ranged from 65 to 92% and this protection was maintained for at least 17 weeks after challenge with the parasite. These findings demonstrate that in heterologous prime/boost immunization approaches, the protocol DNA-LACK/MVA-LACK is superior to DNA-LACK/VV-LACK in triggering specific CD8+ T cell immune responses and in conferring protection against cutaneous leishmaniasis. Thus, MVA-LACK is a safe and efficient vector for vaccination against leishmaniasis.
机译：抗利什曼病的最佳疫苗应引起寄生虫特异性CD4 +和细胞毒性CD8 + T细胞。在这项研究中，我们描述了一种基于DNA和痘病毒载体（Western Reserve，WR，以及高度减毒的改良牛痘病毒Ankara，MVA）的初免/加强免疫方法，它们均表达婴儿利什曼原虫的LACK抗原，并触发不同的水平CD8 + T细胞的特异性反应和对小鼠大肠埃希氏菌感染的保护作用（减少病灶大小和寄生虫病）。与具有复制能力的VV-LACK的类似方案相比，DNA-LACK / MVA-LACK的初次/加强接种疫苗引起更高的CD8 + T细胞反应。通过DNA-LACK / MVA-LACK免疫诱导CD4 +和CD8 + T细胞。来自DNA-LACK / MVA-LACK的脾细胞中的IFN-γ和TNF-α分泌CD8 + T细胞水平高于经DNA-LACK / VV-LACK免疫的动物。此外，当用相同病毒剂量加强免疫时，DNA-LACK / MVA-LACK对大肠埃希氏菌的保护作用明显高于DNA-LACK / VV-LACK免疫动物，并且与高水平的IFN-γ和TNF-α相关分泌CD8 + T细胞。在接种过DNA-LACK / MVA-LACK的动物中，病灶缩小的程度为65％至92％，并且在用寄生虫攻击后，这种保护作用至少维持了17周。这些发现表明，在异源初免/加强免疫方法中，协议DNA-LACK / MVA-LACK在触发特异性CD8 + T细胞免疫应答和赋予针对皮肤利什曼病的保护方面优于DNA-LACK / VV-LACK。因此，MVA-LACK是用于接种针对利什曼病的安全有效的载体。

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