Design of immunogenic and effective multi-epitope DNA vaccines for melanoma.
Design of immunogenic and effective multi-epitope DNA vaccines for melanoma.
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DOI：
10.1007/s00262-011-1110-7
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发表时间：
2012-03
影响因子：
5.8
通讯作者：
Celis, Esteban
中科院分区：
文献类型：
--
作者：
Cho, Hyun-Il;Celis, Esteban
质粒DNA疫苗接种是一种有吸引力的方式来引发针对感染因子和肿瘤细胞的T细胞应答。DNA构建体可以被设计为含有多个T细胞表位以产生多样化的免疫应答，从而将许多抗原并入并减少由于MHC限制而导致的限制性进入单个实体。我们已经制备了cDNA质粒构建体，其中含有几个小鼠T细胞表位连接的弗林蛋白酶敏感或抗性接头，并研究了阳离子细胞穿透序列从HIV-tat的影响。用多表位DNA疫苗，然后进行体内电穿孔，获得显著的CD 8 T细胞应答，而不管所用接头的类型和构建体是否具有HIV-tat序列。免疫应答的幅度与每个疫苗构建体中包含的所有CD 8 T细胞表位非常相似，表明不存在免疫显性。将辅助性T细胞表位插入构建体中增加了T细胞应答。使用含有来自黑素体蛋白的表位的构建体获得了针对B16黑色素瘤的预防性和治疗性抗肿瘤应答，表明这种疫苗接种成功地产生了对自身抗原的应答，所述自身抗原可能受到免疫耐受。这些发现对于设计用于多种疾病的DNA疫苗是有用的，其中T淋巴细胞发挥保护或治疗作用。
Plasmid DNA vaccination is an attractive way to elicit T cell responses against infectious agents and tumor cells. DNA constructs can be designed to contain multiple T cell epitopes to generate a diverse immune response to incorporate numerous antigens and to reduce limitations due to MHC restriction into a single entity. We have prepared cDNA plasmid constructs containing several mouse T cell epitopes connected by either furin-sensitive or resistant linkers, and studied the effects of a cationic cell penetrating sequence from HIV-tat. Significant CD8 T cell responses were obtained with multi-epitope DNA vaccines followed by in vivo electroporation regardless of the type of linker used and whether the construct had the HIV-tat sequence. The magnitude of immune responses was very similar to all CD8 T cell epitopes contained within each vaccine construct indicating the absence of immunodominance. Incorporating a T helper epitope into the constructs increased the T cell responses. Prophylactic and therapeutic anti-tumor responses against B16 melanoma were obtained using a construct containing epitopes from melanosomal proteins, indicating that this vaccination was successful in generating responses to self-antigens that potentially may be subjected to immune tolerance. These findings are useful for designing DNA vaccines for a multitude of diseases where T lymphocytes play a protective or therapeutic role.
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影响因子：
11.2
作者：
Nava-Parada, Pilar;Forni, Guido;Celis, Esteban
通讯作者：
Celis, Esteban
影响因子：
30.5
作者：
Tenzer, Stefan;Wee, Edmund;Iversen, Astrid K. N.
通讯作者：
Iversen, Astrid K. N.
影响因子：
4.4
作者：
Lu, J;Wettstein, PJ;Celis, E
通讯作者：
Celis, E
影响因子：
5.5
作者：
Hanke, T;Neumann, VC;McMichael, A
通讯作者：
McMichael, A
影响因子：
11.2
作者：
Assudani D;Cho HI;DeVito N;Bradley N;Celis E
通讯作者：
Celis E