吡喹酮可以诱导机体干扰素？

MP4

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3187796/

sddp1

百度了下阿德：
阿德福韦可与腺苷酸竞争性掺入病毒DNA链，作为DNA链的终止物抑制DNA聚合酶，终止DNA链的合成，而使病毒的复制受到抑制，还可以诱导内生性α-干扰素，增加自然杀伤细胞(NK)的活力和刺激机体的免疫反应，有较强的抗HIV、HBV及疱疹病毒的作用。

StephenW

PLoS One. 2011; 6(10): e25525. Published online 2011 October 5.   doi:  10.1371/journal.pone.0025525
PMCID: PMC3187796


Praziquantel Facilitates IFN-γ-Producing CD8+ T Cells (Tc1) and IL-17-Producing CD8+ T Cells (Tc17) Responses to DNA Vaccination in Mice
Qiang Zou,1 Xin Yao,2 Jin Feng,3 Zhinan Yin,4 Richard Flavell,5 Yanxin Hu,6 Guoxing Zheng,7 Jin Jin,1 Youmin Kang,1 Bing Wu,1 Xiaoxuan Liang,1 Congcong Feng,1 Hu Liu,1 Weiyi Li,1 Xianzheng Wang,1 Yumei Wen,2 and Bin Wang1,2,*
1State Key Laboratory for Agro-Biotechnology, College of Biological Science, China Agricultural University, Beijing, People's Republic of China
2Key Laboratory of Medical Molecular Virology of MOH and MOE, Fudan University Shanghai Medical College, Shanghai, People's Republic of China
3Center for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, People's Republic of China
4College of Life Sciences, Nankai University, Tianjin, People's Republic of China
5Department of Immunobiology, Yale School of Medicine, New Haven, Conneticut, United States of America
6College of Veterinary Medicine, China Agricultural University, Beijing, People's Republic of China
7Department of Biomedical Sciences, University of Illinois College of Medicine, Rockford, Illinois, United States of America
* E-mail: [email protected]


Abstract
Background

CD8+ cytotoxic T lymphocytes (CTLs) are crucial for eliminating hepatitis B virus (HBV) infected cells. DNA vaccination, a novel therapeutic strategy for chronic virus infection, has been shown to induce CTL responses. However, accumulated data have shown that CTLs could not be effectively induced by HBV DNA vaccination.

Methodology/Principal Findings

Here, we report that praziquantel (PZQ), an anti-schistoma drug, could act as an adjuvant to overcome the lack of potent CTL responses by HBV DNA vaccination in mice. PZQ in combination with HBV DNA vaccination augmented the induction of CD8+ T cell-dependent and HBV-specific delayed hypersensitivity responses (DTH) in C57BL/6 mice. Furthermore, the induced CD8+ T cells consisted of both Tc1 and Tc17 subtypes. By using IFN-γ knockout (KO) mice and IL-17 KO mice, both cytokines were found to be involved in the DTH. The relevance of these findings to HBV immunization was established in HBsAg transgenic mice, in which PZQ also augmented the induction of HBV-specific Tc1 and Tc17 cells and resulted in reduction of HBsAg positive hepatocytes. Adoptive transfer experiments further showed that PZQ-primed CD8+ T cells from wild type mice, but not the counterpart from IFN-γ KO or IL-17 KO mice, resulted in elimination of HBsAg positive hepatocytes.

Conclusions/SignificanceOur results suggest that PZQ is an effective adjuvant to facilitate Tc1 and Tc17 responses to HBV DNA vaccination, inducing broad CD8+ T cell-based immunotherapy that breaks tolerance to HBsAg

CD8 +细胞毒性T淋巴细胞（CTL）的消除乙肝病毒（HBV）感染细胞的关键。已经表明，慢性病毒感染的一种新的治疗策略，DNA疫苗诱导CTL反应。但是，积累的数据表明，淋巴细胞不能有效地诱导HBV DNA疫苗。
方法/主要结果

在这里，我们报告说，吡喹酮（PZQ），的反schistoma药物，可作为辅助，以克服由乙型肝炎病毒DNA疫苗在小鼠体内缺乏强有力的CTL反应。 PZQ增强结合HBV DNA疫苗诱导的CD8 + T细胞依赖性和HBV特异性迟发型超敏反应反应（DTH）的在C​​57BL / 6小鼠。此外，诱导CD8 + T细胞Tc1和TC17亚型。使用γ-干扰素基因敲除（KO）小鼠IL-17 KO小鼠，两种细胞因子被发现在参与的DTH。这些研究结果的相关性乙肝疫苗接种，建立HBsAg转基因小鼠，PZQ在这也增加了诱导的HBV特异性TC1，TC17细胞导致HBsAg阳性肝细胞减少。继转移实验进一步表明，PZQ的引物从野生型小鼠的CD8 + T细胞，但不是从γ-干扰素KO或IL-17 KO小鼠的对口，导致在消除乙肝表面抗原阳性的肝细胞。
结论/意义

我们的研究结果表明PZQ是一种有效的辅助，以促进Tc1和TC17 HBV DNA疫苗的反应，引起广泛的CD8 + T细胞为基础的免疫疗法，打破容忍对HBsAg

StephenW

看起是闻玉梅教授DNA疫苗的研究,到目前为止，仅在小鼠模型.

MP4

StephenW 发表于 2012-7-7 14:52
看起是闻玉梅教授DNA疫苗的研究,到目前为止，仅在小鼠模型.

http://www.cau.edu.cn/bwlab/chs/interests.htm
闻只是协作吧，看了下主要是中国农业大学农业生物技术国家重点实验室王宾教授分子免疫学实验室做的。

主要是吡喹酮有没利用价值，虽然吡喹酮可能停产了，但是很早前已是可治肝吸虫肝硬化的药。
临床前的治疗性乙肝疫苗多着啊，估计不久还有新的疫苗批准临床试验，这我不想太多了。近期内比较实际的，关键是怎么使，怎样更高效产生干扰素爬坡，量变才能质变。

MP4

sddp1 发表于 2012-7-7 14:21
百度了下阿德：
阿德福韦可与腺苷酸竞争性掺入病毒DNA链，作为DNA链的终止物抑制DNA聚合酶，终止DNA链的合 ...

有些时候我会考虑什么病毒和HBV相同点比较多。
例如很多对HIV有效的，有些对HBV也有效。不过HBV是DNA病毒，HIV是RNA病毒，相距还是太远。

咬牙硬挺

无敌抗体

P4,一直很关注你，能不能介绍一下您自己？

MP4

无敌抗体 发表于 2012-7-8 13:28
P4,一直很关注你，能不能介绍一下您自己？

就普通人一个咯，又不是医生。
你想了解些啥？

sddp1

回复 MP4 的帖子

dna病毒的生命周期中会有dna→RNA的过程。甚至RNA可以通过逆转录酶合成dna。从某种意义上说dna病毒和RNA病毒是亲戚，就像我们人类和猴子一样在生命进化树中血缘相近。