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基于DNA免疫后,CpG免疫刺激基序增强针对丙型肝炎病毒核心蛋白的体液免疫反应。

CpG immuno-stimulatory motifs enhance humoral immune responses against hepatitis C virus core protein after DNA-based immunization.

作者信息

Encke J, zu Putlitz J, Stremmel W, Wands J R

机构信息

Molecular Hepatology Laboratory, Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts, U.S.A.

出版信息

Arch Virol. 2003 Mar;148(3):435-48. doi: 10.1007/s00705-002-0935-y.

Abstract

Chronic HCV infection is associated with a high morbidity and mortality rate, and currently a prophylactic or therapeutic vaccine is not available. DNA-based immunization is a powerful method to generate cellular and humoral immune responses. However, DNA immunization against HCV core results only in a weak humoral immune response demonstrated in several studies. Therefore, co-immunization with a novel adjuvant may enhance such potentially important immune responses. We examined whether unmethylated CpG motifs in the form of oligodeoxynucleotides (ODN) or E. coli DNA can act as adjuvants for a DNA vaccination approach, since CpG motifs have been shown to stimulate the innate immune system as well as B and T cell immune reactivity. The present study demonstrates that CpG motifs enhance in vivo antibody levels after DNA immunization against HCV core. However, despite some in vitro activity of CpG motifs, no enhancement of T cell responses in vivo was observed after immunization with HCV plasmid DNA and CpG motifs in mice. Our results suggest that co-immunization with CpG-ODN may strengthen humoral immune responses but show no potential effect as an adjuvant to induce cellular immunity against HCV core.

摘要

慢性丙型肝炎病毒(HCV)感染与高发病率和死亡率相关,目前尚无预防性或治疗性疫苗。基于DNA的免疫接种是产生细胞免疫和体液免疫反应的有效方法。然而,多项研究表明,针对HCV核心抗原的DNA免疫接种仅能引发微弱的体液免疫反应。因此,与新型佐剂共同免疫接种可能会增强这种潜在的重要免疫反应。我们研究了以寡脱氧核苷酸(ODN)或大肠杆菌DNA形式存在的未甲基化CpG基序是否可作为DNA疫苗接种方法的佐剂,因为CpG基序已被证明能刺激先天免疫系统以及B细胞和T细胞的免疫反应性。本研究表明,CpG基序可提高针对HCV核心抗原的DNA免疫接种后的体内抗体水平。然而,尽管CpG基序在体外有一定活性,但在用HCV质粒DNA和CpG基序对小鼠进行免疫接种后,未观察到体内T细胞反应增强。我们的结果表明,与CpG-ODN共同免疫接种可能会增强体液免疫反应,但作为诱导针对HCV核心抗原的细胞免疫的佐剂没有潜在效果。

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