Volume 134, Issue 5, Pages 1385-1395.e1 (May 2008) Therapeutic Vaccination of Chronic Hepatitis C Nonresponder Patients With the Peptide Vaccine IC41  Christoph S. Klade, Heiner Wedemeyer, Thomas Berg, Holger Hinrichsen, Grazyna Cholewinska, Stefan Zeuzem, Hubert Blum, Michael Buschle, Sandra Jelovcan, Vera Buerger, Erich Tauber, Juergen Frisch, Michael P. Manns  Gastroenterology  Volume 134, Issue 5, Pages 1385-1395.e1 (May 2008) DOI: 10.1053/j.gastro.2008.02.058 Copyright © 2008 AGA Institute Terms and Conditions

Figure 1 Primary end point immunogenicity: CD4+ T-cell proliferation. (A) Responder rates per dose group. Up to 67% of patients responded to the optimal IC41 dose, whereas only 17% responded to the peptide only vaccinations. (B) Median of HCV specific CD4+ T-cell proliferation (sum stimulation index [SI] of the 3 class II peptides in IC41) per dose group (ITT population) over time. Gastroenterology 2008 134, 1385-1395.e1DOI: (10.1053/j.gastro.2008.02.058) Copyright © 2008 AGA Institute Terms and Conditions

Figure 2 IC41 but not peptide (or adjuvant) alone induces IFN-γ secreting T cells in chronic HCV patients: up to one third of patients (4 out of 12) treated with the optimal dose of IC41 developed significant IFN-γ responses to the 3 class II CD4 + T-cell epitopes contained in the vaccine. One quarter of patients (3 out of 12) showed CD4+ T helper responses and responses to the 4 class I CD8 + T-cell epitopes. Gastroenterology 2008 134, 1385-1395.e1DOI: (10.1053/j.gastro.2008.02.058) Copyright © 2008 AGA Institute Terms and Conditions

Figure 3 Correlation of HCV RNA responses and T-cell responses. (A) Mean viral load per dose group. (B) Individual RNA time course in >1 log RNA responders (patients 3013, 4001, 5001). (C and D) Correlation of HCV RNA, liver enzymes, and ELIspot time course in patients 4001 (C) and 3013 (D). (E) Flow cytometry plots and intracellular cytokine stainings for patient 3013. Gastroenterology 2008 134, 1385-1395.e1DOI: (10.1053/j.gastro.2008.02.058) Copyright © 2008 AGA Institute Terms and Conditions

Figure 3 Correlation of HCV RNA responses and T-cell responses. (A) Mean viral load per dose group. (B) Individual RNA time course in >1 log RNA responders (patients 3013, 4001, 5001). (C and D) Correlation of HCV RNA, liver enzymes, and ELIspot time course in patients 4001 (C) and 3013 (D). (E) Flow cytometry plots and intracellular cytokine stainings for patient 3013. Gastroenterology 2008 134, 1385-1395.e1DOI: (10.1053/j.gastro.2008.02.058) Copyright © 2008 AGA Institute Terms and Conditions