Therapeutic vaccination of chronic hepatitis C nonresponder patients with the peptide vaccine IC41

May 26, 2008

Gastroenterology. 2008 May;134(5):1385-95. Epub 2008 Mar 4.

Therapeutic vaccination of chronic hepatitis C nonresponder patients with the

peptide vaccine IC41.

Klade CS, Wedemeyer H, Berg T, Hinrichsen H, Cholewinska G, Zeuzem S, Blum H,

Buschle M, Jelovcan S, Buerger V, Tauber E, Frisch J, Manns MP.

Intercell AG, Vienna, Austria.

BACKGROUND & AIMS: 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.

PMID: 18471515 [PubMed - in process]

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