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首页> 外文期刊>World Journal of Gastroenterology >Genetic vaccination with Flt3-L and GM-CSF as adjuvants: Enhancement of cellular and humoral immune responses that results in protective immunity in a murine model of hepatitis C virus infection.
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Genetic vaccination with Flt3-L and GM-CSF as adjuvants: Enhancement of cellular and humoral immune responses that results in protective immunity in a murine model of hepatitis C virus infection.

机译：以Flt3-L和GM-CSF作为佐剂的基因疫苗接种：增强细胞和体液免疫反应，从而在丙型肝炎病毒感染的小鼠模型中产生保护性免疫。

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AIM: To investigate whether transfection of plasmid DNA encoding these cytokines enhances both humoral and cellular immune responses to hepatitis C virus (HCV) in a murine model. METHODS: We established a tumor model of HCV infection using syngenic mouse myeloma cells stably transfected with NS5. Co-vaccination of DNA encoding granulocyte macrophage colony-stimulating factor (GM-CSF) and Flt-3 ligand together with a plasmid encoding for the HCV NS5 protein was carried out. Mice were sacrificed 14 d after the last immunization event with collection of spleen cells and serum to determine humoral and cellular immune responses. RESULTS: Co-vaccination of DNA encoding GM-CSF and Flt-3 ligand together with a plasmid encoding for the HCV NS5 protein induced increased antibody responses and CD4+ T cell proliferation to this protein. Vaccination with DNA encoding GM-CSF and Flt-3L promoted protection against tumor formation and/or reduction in mice co-immunized with cytokine-encoding DNA constructs. This suggests this strategy is capable of generating cytotoxic T lymphocyte activity in vivo. Following inoculation with plasmid DNA encoding Flt-3L, no increase in spleen size or in dendritic cell (DC) and natural killer cell numbers was observed. This was in contrast to a dramatic increase of both cell types after administration of recombinant Flt3-L in vivo. This suggests that vaccination with plasmid DNA encoding cytokines that regulate DC generation and mobilization may not promote unwanted side effects, such as autoimmunity, splenic fibrosis or hematopoietic malignancies that may occur with administration of recombinant forms of these proteins. CONCLUSION: Our data support the view that plasmid DNA vaccination is a promising approach for HCV immunization, and may provide a general adjuvant vaccination strategy against malignancies and other pathogens.
机译：目的：研究在鼠模型中转染编码这些细胞因子的质粒DNA是否能增强对丙型肝炎病毒（HCV）的体液和细胞免疫应答。方法：我们使用稳定转染NS5的同基因小鼠骨髓瘤细胞建立了HCV感染的肿瘤模型。将编码粒细胞巨噬细胞集落刺激因子（GM-CSF）和Flt-3配体的DNA与编码HCV NS5蛋白的质粒一起接种疫苗。在最后一次免疫事件后14天处死小鼠，收集脾细胞和血清以确定体液和细胞免疫应答。结果：编码GM-CSF和Flt-3配体的DNA与编码HCV NS5蛋白的质粒一起接种疫苗诱导了对该蛋白的抗体应答和CD4 + T细胞增殖的增加。用编码GM-CSF和Flt-3L的DNA进行疫苗接种可增强针对编码细胞因子的DNA构建体共免疫的小鼠的肿瘤形成和/或减少的保护作用。这表明该策略能够在体内产生细胞毒性T淋巴细胞活性。接种编码Flt-3L的质粒DNA后，未观察到脾脏大小或树突状细胞（DC）和自然杀伤细胞数目增加。这与在体内施用重组Flt3-L后两种细胞类型的急剧增加相反。这表明用编码调节DC产生和动员的细胞因子的质粒DNA进行的疫苗接种可能不会促进不良副作用，例如自身免疫，脾纤维化或造血性恶性肿瘤，这些副作用可能会因重组蛋白形式出现。结论：我们的数据支持这样一种观点，即质粒DNA疫苗接种是HCV免疫的一种有前途的方法，并可能提供针对恶性肿瘤和其他病原体的一般佐剂疫苗接种策略。

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