Candida skin test reagent as a novel adjuvant for a human papillomavirus peptide-based therapeutic vaccine.
Candida skin test reagent as a novel adjuvant for a human papillomavirus peptide-based therapeutic vaccine.
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DOI：
10.1016/j.vaccine.2013.10.014
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发表时间：
2013-12-02
期刊：
影响因子：
5.5
通讯作者：
Nakagawa, Mayumi
中科院分区：
文献类型：
--
作者：
Wang, Xuelian;Coleman, Hannah N.;Nagarajan, Uma;Spencer, Horace J.;Nakagawa, Mayumi
目前尚无能够有效促进细胞免疫的疫苗佐剂。由于念珠菌皮试试剂注射液能够诱导寻常疣消退，我们的小组将其用作基于肽的人乳头瘤病毒治疗性疫苗的临床试验中的新型佐剂。本研究的目的是调查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的成熟效应、T 细胞增殖能力、朗格汉斯细胞细胞因子和模式识别受体的表达以及诱导 Th1、Th2 和 Th17 反应的能力。该疫苗是含有念珠菌的人乳头瘤病毒肽，对朗格汉斯细胞具有部分成熟作用，表现为 CD40 (p=0.00007) 和 CD80 (p<0.00001) 水平显着上调，并且在体外由朗格汉斯细胞呈递时显示出 T 细胞增殖能力 (p<0.00001)。有趣的是，成熟效应是由肽引起的，而念珠菌则负责 T 细胞增殖。用疫苗或单独念珠菌处理的朗格汉斯细胞的细胞因子谱（IL-1β、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。所有受试者中均存在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）。另一方面，仅在一名受试者中证实了用疫苗刺激的 CD4 细胞或念珠菌脉冲的朗格汉斯细胞分泌 IFN-γ 诱导 Th1 应答。综上所述，疫苗的朗格汉斯细胞成熟作用来自肽，T细胞增殖能力来自念珠菌，最常诱导的细胞因子是IL-12。
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-1β, IL-6, IL-8, IL-10, IL-12p40, IL-23Ap19, IFN-γ, and TNF-α) 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-γ 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.
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影响因子：
4.4
作者：
Jouault, Thierry;Behi, Miryam El Abed-El;Poulain, Daniel
通讯作者：
Poulain, Daniel
影响因子：
1.5
作者：
Clifton, MM;Johnson, SM;Horn, TD
通讯作者：
Horn, TD
影响因子：
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作者：
Netea, Mihai G.;van de Veerdonk, Frank;Kullberg, Bart Jan
通讯作者：
Kullberg, Bart Jan
DOI：
10.1111/igc.0b013e3181a388c4
发表时间：
2009-05
期刊：
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
影响因子：
--
作者：
Farhat S;Nakagawa M;Moscicki AB
通讯作者：
Moscicki AB
DOI：
10.1126/science.1183021
发表时间：
2010-01-15
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
Iwasaki A;Medzhitov R
通讯作者：
Medzhitov R