MVA-LACK as a safe and efficient vector for vaccination against leishmaniasis
MVA-LACK as a safe and efficient vector for vaccination against leishmaniasis
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DOI：
10.1016/j.micinf.2005.10.004
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发表时间：
2006-03-01
影响因子：
5.8
通讯作者：
Esteban, Mariano
中科院分区：
文献类型：
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作者：
Perez-Jimenez, Eva;Kochan, Grazyna;Esteban, Mariano
针对利什曼病的最佳疫苗应诱导寄生虫特异性CD 4+和细胞毒性CD 8 + 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和高度减毒的改良牛痘病毒Ankara，MVA）的初免/加强免疫方法，两者都表达婴儿利什曼原虫的LACK抗原，触发不同水平的特异性CD 8 + T细胞应答和保护（减少病变大小和寄生虫血症）。小鼠的主要感染。用DNA-LACK/MVA-LACK的初免加强疫苗接种比用复制型VV-LACK的类似方案产生更高的CD 8 + T细胞应答。通过DNA-LACK/MVA-LACK免疫诱导CD 4+和CD 8 + T细胞。分泌IFN-γ和TNF-α的CD 8 + T细胞的水平在来自DNA-LACK/MVA-LACK的脾细胞中高于DNA-LACK/VV-LACK免疫的动物中。此外，对L.当用相同病毒剂量加强时，DNA-LACK/MVA-LACK免疫的动物中的major显著高于DNA-LACK/VV-LACK免疫的动物，并且与高水平的IFN-γ和TNF-α分泌性CD 8 + T细胞相关。在DNA-LACK/MVA-LACK接种的动物中，病变尺寸减小的程度范围为65%至92%，并且在用寄生虫攻击后这种保护维持至少17周。这些发现表明，在异源初免/加强免疫方法中，方案DNA-LACK/MVA-LACK在触发特异性CD 8 + 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上级。因此，MVA-LACK是用于针对利什曼病的疫苗接种的安全且有效的载体。(c)2005年，Elsevier SAS。All rights reserved.
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 primelboost 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 vir-us 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. (c) 2005 Elsevier SAS. All rights reserved.