Immunological monitoring during therapeutic vaccination...

liver411

Vaccine, Vol. 20 (29-30) (2002) pp. 3598-3612
© 2002 Elsevier Science Ltd. All rights reserved.
PII: S0264-410X(02)00309-2

Immunological monitoring during therapeutic vaccination as a prerequisite for the design of new effective therapies: induction of a vaccine-specific CD4+ T-cell proliferative response in chronic hepatitis B carriers
Maria-Christina Jung a,b * [email protected] , Norbert Grüner a,b, Reinhart Zachoval a, Winfried Schraut b, Tilman Gerlach a,b, Helmut Diepolder a,b, Carl-Albrecht Schirren a, Mark Page c, John Bailey c, Emma Birtles c, Eve Whitehead c, Jörg Trojan d, Stefan Zeuzem d and Gerd R. Pape a,b
a Medical Department II, Klinikum Großhadern, University of Munich, Marchioninistrasse 15, 81377 Munich, Germany
b Institute for Immunology, University of Munich, Goethestrasse 31, 80336 Munich, Germany
c Medeva Development, Medeva Pharma Limited, Medeva House, Regent Park, Kingston Road, Leatherhead, Surrey KT227PQ, UK
d Medical Department II, Klinikum der Johann Wolfgang Goethe-Universität, University of Frankfurt, Frankfurt, Germany
Received 6 June 2002; accepted 6 June 2002

Abstract
We characterized the anti-viral T-cell response in 22 chronically infected patients, who participated in a European multi-center randomized placebo-controlled, double-blind study therapeutic vaccination trial with pre-S1, pre-S2 and S antigenic components of the hepatitis B virus (HBV). It induced a significant HBsAg-specific T-cell proliferation and the production of Th2-cytokines (i.e. IL-5). A specific induction of Th1-lymphokines was not detectable although this has been demonstrated in this study in response to the nucleocapsid protein (HBcAg). Further analysis indicated that this approach does not activate HBV-specific CD8+ T-lymphocytes as detected by ELISPOT-assay. Our results might explain why a specific therapeutic vaccine, although safe and well-tolerated is not always able to break tolerance leading to the clearance of the hepatitis B virus.

Keywords: Therapeutic vaccine; Induction of T-cell response; Treatment in chronic HBV infection
*Corresponding author. Tel.: +49-89-70950; fax: +49-89-70009540.

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© Copyright 2002, Elsevier Science, All rights reserved.

life

在治疗性乙肝疫苗使用过程中的免疫学监测是设计新的有效的治疗方案的先决条件：在慢性乙肝患者体内进行 诱导疫苗特异性的CD4+的T细胞的扩增的研究。

摘要：
在22个慢性乙肝患者中对抗病毒的T细胞反应进行了研究。研究治疗性乙肝疫苗（hbv的前S1,前S2和S抗原组分），发现治疗性乙肝疫苗诱导HBsAg特异性的T细胞显著扩增，并产生Th2细胞因子（如IL-5），然而并未检测到HBcAg特异性的Th1淋巴因子。更进一步的分析，用ELISPOT方法检测发现治疗性乙肝疫苗不能激活对HBV有特异性反应的CD8+的T淋巴细胞。我们的结果部分的解释了为什么特异治疗性乙肝疫苗安全而且副作用小，但是并不总能清除HBV的原因。

不太好理解，因此找到原文看了一下，

在慢性HBV感染中弱的抗病毒T细胞应答是与持续的病毒存在相联系的，
在急性HBV患者中，HBsAg的消失和血清中表面抗体（抗HBs）的出现
标志着病毒的清除并且病人体内出现了保护性的免疫反应，然而在慢性
HBV患者中这种表面抗体通常难以检测。在体外实验中，目前还不了解
慢性HBV携带者是否有HBsAg特异性的Th的缺陷，因为不管是在慢性或
者急性乙肝患者中对HBsAg应答的T细胞扩增非常少或者难以检测.

这篇文章对检测方法进行了研究和分析，设计了一个检测方法，作为有效
的治疗方案的辅助工具