Immunogenicity and safety of a novel therapeutic hepatitis C virus (HCV) peptide vaccine: A randomized, placebo controlled trial for dose optimization in 128 healthy subjects

• Published in: Vaccine Vol. 24; no. 20; pp. 4343 - 4353
• Main Authors: Firbas, Christa, Jilma, Bernd, Tauber, Erich, Buerger, Vera, Jelovcan, Sandra, Lingnau, Karen, Buschle, Michael, Frisch, Jürgen, Klade, Christoph S.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15.05.2006; Elsevier; Elsevier Limited
• Subjects: Adolescent; Adult; Applied microbiology; Biological and medical sciences; Cell growth; Chronic illnesses; Fundamental and applied biological sciences. Psychology; Hepatitis; Hepatitis C; Hepatitis C - prevention & control; Hepatitis C virus; Human; Human viral diseases; Humans; Immunogenicity; Infections; Infectious diseases; Interferon-gamma - biosynthesis; Lymphocytes; Medical sciences; Microbiology; Middle Aged; Miscellaneous; Mortality; Optimization; Peptide vaccine; Peptides; Placebos; Proteins; Randomized controlled trial; Reference Values; Single-Blind Method; T-Lymphocytes - metabolism; T-Lymphocytes - pathology; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Viral diseases; Viral hepatitis; Viral Vaccines - adverse effects; Viral Vaccines - immunology; Virology; United States > US; Human; Peptide vaccine; Hepatitis C; Randomized controlled trial; Hepatitis A virus; Peptides; Picornaviridae; Toxicity; Hepatic disease; Vaccine; Optimization; Hepatovirus; Infection; Virus; Immunogenicity; Viral disease; Digestive diseases; Flaviviridae; Hepatitis C virus; Hepacivirus; Viral hepatitis C
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2006.03.009

As interferon/ribavirin-based standard therapy is curative in only about half of HCV patients, there remains an important need for alternatives including vaccines. The novel peptide vaccine IC41 consists of five synthetic peptides harboring HCV T cell epitopes and poly- l-arginine as synthetic adjuvant. In this randomized, placebo-controlled trial, 128 HLA-A2 positive healthy volunteers received four s.c. vaccinations of seven different doses IC41, HCV peptides alone, poly- l-arginine alone or saline solution, every 4 weeks. IC41 was safe and well tolerated. Mild to moderate local reactions were transient. Immunogenicity was assessed using T cell epitope specific [ 3H]-thymidine proliferation, IFN-gamma ELIspot and HLA-tetramer assays. IC41 induced responses in all dose groups. Higher responder rates were recorded in higher dose groups and increasing number of vaccinations were associated with higher responder rates and more robust responses. Poly- l-arginine was required for the aimed-for Th1/Tc1-type immunity (IFN-gamma secreting T cells).