Plasmids encoding granulocyte-macrophage colony-stimulating factor and CD154 enhance the immune response to genetic vaccines.
Plasmids encoding granulocyte-macrophage colony-stimulating factor and CD154 enhance the immune response to genetic vaccines.
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编码粒细胞-巨噬细胞集落刺激因子和 CD154 的质粒可增强对基因疫苗的免疫反应。
DOI：
10.1016/s0264-410x(00)00382-0
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发表时间：
2001
期刊：
影响因子：
5.5
通讯作者：
Kipps,TJ
中科院分区：
文献类型：
--
作者：
Burger,JA;Mendoza,RB;Kipps,TJ
我们研究了编码粒细胞-巨噬细胞集落刺激因子（pGM-CSF）或CD 40-配体（pCD 40 L）的质粒是否可以改变对共注射质粒DNA编码的抗原的免疫应答。为此，我们使用由质粒pLacZ编码的土方嗜酸乳杆菌β半乳糖苷酶（β-gal）作为抗原。我们发现，皮内共注射pLacZ与pGM-CSF和pCD 40 L两者与单独注射pLacZ相比将抗β-gal IgG应答增强约两个数量级。与pLacZ和pGM-CSF或pCD 40 L共注射的动物相比，pGM-CSF和pCD 40 L与pLacZ共注射显著增强了抗原特异性IgG，特别是IgG 2a。我们发现，pGM-CSF和pCD 40 L与pLacZ的共注射增强了β-gal特异性细胞毒性T细胞的产生，并且允许从与表达β-gal的刺激细胞共培养的脾细胞显著扩增CD 8 +T细胞。pGM-CSF或pCD 40 L诱导的免疫刺激作用需要将这些质粒注射到接受pLacZ的同一位点。“致敏”实验（其中注射部位预先注射任一种质粒佐剂）显示pGM-CSF而不是pCD 40 L可增强随后施用的质粒抗原诱导的抗β-gal免疫应答。我们得出结论，编码GM-CSF和CD 154的质粒是特别有效的遗传佐剂，当一起使用，以增强体液和细胞免疫应答的质粒编码的抗原。
We examined whether plasmids encoding granulocyte–macrophage colony-stimulating factor (pGM-CSF) or CD40-ligand (pCD40L) could modify the immune response to antigen encoded by co-injected plasmid DNA. For this we used as antigen Escherichiacoli β galactosidase (β-gal), encoded by the plasmid pLacZ. We found that intradermal co-injection of pLacZ with both pGM-CSF and pCD40L enhanced the anti-β-gal IgG response by approximately two orders of magnitude compared to injections of pLacZ alone. Co-injection of both pGM-CSF and pCD40L with pLacZ significantly enhanced antigen-specific IgG, and in particular IgG2a, over that of animals co-injected with pLacZ and either pGM-CSF or pCD40L. We found that co-injection of pGM-CSF and pCD40L with pLacZ enhanced the generation of β-gal-specific cytotoxic T cells, and allowed for a significant expansion of CD8+T cells from splenocytes co-cultured with β-gal expressing stimulator cells. The immunostimulatory effects induced by pGM-CSF or pCD40L required injection of these plasmids to the same site that received pLacZ. ‘Priming’ experiments, where the site of injection was pre-injected with either plasmid adjuvant, showed that pGM-CSF, but not pCD40L, could enhance the anti-β-gal immune response induced by subsequently administered plasmid antigen. We conclude that plasmids encoding GM-CSF and CD154 are particularly effective genetic adjuvants when used together to enhance the humoral and cellular immune response to a plasmid-encoded antigen.
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影响因子：
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作者：
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通讯作者：
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