Therapeutic vaccination of chronic hepatitis C nonresponder patients with the peptide vaccine IC41.
OBJECTIVE
IC41 is a synthetic peptide vaccine containing 7 relevant hepatitis C virus (HCV) T-cell epitopes and the T helper cell (Th)1/Tc1 adjuvant poly-L-arginine. IC41 has been shown to be safe and to induce HCV-specific interferon (IFN)-gamma-secreting CD4+ and CD8+ T cells in healthy volunteers. We aimed to investigate whether IC41 is able to induce HCV-specific T-cell responses also in chronic hepatitis C patients.


METHODS
Sixty HLA-A2-positive chronic HCV patients not responding to or relapsing from standard therapy were randomized in a double-blind phase II study into 5 groups to receive 6 vaccinations of IC41 (3 different dose groups), HCV peptides alone, or poly-L-arginine alone.


RESULTS
IC41 was well tolerated, and no drug-related serious adverse events or induction of hepatitis were observed. T-cell proliferation was recorded in up to 67% of patients in the 3 IC41 vaccine groups but only in 17% of patients treated with peptides alone. IFN-gamma enzyme-linked immunospot assay responses were observed exclusively in the IC41 groups with response rates up to 42%. There were 3 RNA responders with transient >1-log declines of HCV serum RNA associated with the strongest IFN-gamma enzyme-linked immunospot assay values within all 60 patients.


CONCLUSIONS
This study showed that the HCV peptide vaccine IC41 can induce HCV-specific Th1/Tc1 responses in a subset of difficult to treat HCV nonresponder patients despite persisting viremia. However, changes in HCV RNA occurred only in single patients. Because strongest T-cell responses were associated with HCV RNA decline, further studies with optimized vaccine regimens and combination therapies have been initiated.
Klade
Christoph S
CS
Intercell AG, Vienna, Austria.
Wedemeyer
Heiner
H
Berg
Thomas
T
Hinrichsen
Holger
H
Cholewinska
Grazyna
G
Zeuzem
Stefan
S
Blum
Hubert
H
Buschle
Michael
M
Jelovcan
Sandra
S
Buerger
Vera
V
Tauber
Erich
E
Frisch
Juergen
J
Manns
Michael P
MP
D000328:Adult; D000368:Aged; D016516:CD4-CD8 Ratio; D049109:Cell Proliferation; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000628:therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods*; D022223:Vaccines, Subunit; D014765:Viral Vaccines / Q000627:therapeutic use*
D012367:RNA, Viral; D022223:Vaccines, Subunit; D014765:Viral Vaccines