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发表于 2002-11-7 17:18
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.
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