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首页> 外文期刊>Vaccine >Candida skin test reagent as a novel adjuvant for a human papillomavirus peptide-based therapeutic vaccine.
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Candida skin test reagent as a novel adjuvant for a human papillomavirus peptide-based therapeutic vaccine.

机译:念珠菌皮肤测试试剂作为基于人乳头瘤病毒肽的治疗性疫苗的新型佐剂。

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A vaccine adjuvant that can effectively promote cell-mediated immunity is currently not available. Because of the ability of a Candida skin test reagent injection to induce common wart regression, our group is using it as a novel adjuvant in a clinical trial of a peptide-based human papillomavirus therapeutic vaccine. The goal of this current study was to investigate the mechanisms of how Candida enhances the vaccine immune responses. Maturation effects on Langerhans cells, capacity to proliferate T-cells, expression of cytokines and pattern recognition receptors by Langerhans cells, and ability to induce Th1, Th2, and Th17 responses were investigated in healthy subjects. The vaccine, human papillomavirus peptides with Candida, demonstrated partial maturation effects on Langerhans cells indicated by significantly up-regulated CD40 (p=0.00007) and CD80 (p<0.00001) levels, and showed T-cell proliferative capacity (p<0.00001) when presented by Langerhans cells in vitro. Interestingly, the maturation effects were due to the peptides while Candida was responsible for the T-cell proliferation. The cytokine profile (IL-1 beta , IL-6, IL-8, IL-10, IL-12p40, IL-23Ap19, IFN- gamma and TNF- alpha ) of Langerhans cells treated with the vaccine or Candida alone showed that IL-12p40 mRNA was most frequently induced, and IL-12p70 protein was detected in the supernatants. The presence of pattern recognition receptors known to associate with Candida albicans (DC-SIGN, dectin-1, dectin-2, galectin-3, mincle, mannose receptor, Toll-like receptors-1, 2, 4, 6 and 9) were demonstrated in all subjects. On the other hand, the induction of Th1 response demonstrated by IFN- gamma secretion by CD4 cells stimulated with the vaccine or Candida pulsed Langerhans cells was demonstrated only in one subject. In summary, the Langerhans cell maturation effects of the vaccine were due to the peptides while the T-cell proliferative capacity was derived from Candida, and the most frequently induced cytokine was IL-12.
机译:目前尚无能有效促进细胞介导的免疫的疫苗佐剂。由于念珠菌皮肤测试试剂注射具有诱导普通疣消退的能力,因此我们小组在基于肽的人乳头瘤病毒治疗性疫苗的临床试验中将其用作新型佐剂。这项当前研究的目的是研究念珠菌如何增强疫苗免疫反应的机制。在健康受试者中,研究了朗格汉斯细胞对成熟的影响,朗格汉斯细胞增殖T细胞的能力,朗格汉斯细胞表达的细胞因子和模式识别受体以及诱导Th1,Th2和Th17反应的能力。该疫苗是带有念珠菌的人乳头瘤病毒肽,通过显着上调CD40(p = 0.00007)和CD80(p <0.00001)的水平表现出对Langerhans细胞的部分成熟作用,并在出现T细胞增殖能力时(p <0.00001)由Langerhans细胞在体外提供。有趣的是,成熟效果是由于肽引起的,而念珠菌负责T细胞的增殖。单独使用疫苗或念珠菌治疗的朗格汉斯细胞的细胞因子谱(IL-1 beta,IL-6,IL-8,IL-10,IL-12p40,IL-23Ap19,IFN-γ和TNF-α)显示IL -12p40 mRNA最常被诱导,并且在上清液中检测到IL-12p70蛋白。已知与白色念珠菌相关的模式识别受体(DC-SIGN,dectin-1,dectin-2,galectin-3,mincle,甘露糖受体,Toll样受体-1、2、4、6和9)的存在在所有科目中都得到证明。另一方面,仅在一个受试者中证明了用疫苗或念珠菌脉冲的朗格汉斯细胞刺激的CD4细胞通过IFN-γ分泌证明的Th1应答的诱导。总而言之,疫苗的朗格汉斯细胞成熟作用是由于肽引起的,而T细胞的增殖能力则来自假丝酵母,最常诱导的细胞因子是IL-12。

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