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.
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.
Jung
Maria-Christina
MC
Medical Department II, Klinikum Grosshadern, University of Munich, Marchioninistrasse 15, 81377, Munich, Germany. maria-christina.jung@med2.med.uni-muenchen.de
Grüner
Norbert
N
Zachoval
Reinhart
R
Schraut
Winfried
W
Gerlach
Tilman
T
Diepolder
Helmut
H
Schirren
Carl-Albrecht
CA
Page
Mark
M
Bailey
John
J
Birtles
Emma
E
Whitehead
Eve
E
Trojan
Jörg
J
Zeuzem
Stefan
S
Pape
Gerd R
GR
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004279:DNA, Viral / Q000032:analysis; D004311:Double-Blind Method; D005260:Female; D006512:Hepatitis B Core Antigens / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000627:therapeutic use*; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination
D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D017325:Hepatitis B Vaccines; D007376:Interleukin-2; D015848:Interleukin-5; D016753:Interleukin-10; D007371:Interferon-gamma; D000410:Alanine Transaminase