title: Immunogenicity and safety of different injection routes and schedules of IC41, a Hepatitis C virus (HCV) peptide vaccine.
abstract: BACKGROUND
  An effective vaccine would be a significant progress in the management of chronic HCV infections. This study was designed to examine whether different application schedules and injection routes may enhance the immunogenicity of the HCV peptide vaccine IC41.
  
  
  METHODS
  In this randomized trial 54 healthy subjects received either subcutaneous (s.c.) or intradermal (i.d.) vaccinations weekly (16 injections) or every other week (8 injections). One group additionally received imiquimod, an activator of the toll-like receptor (TLR) 7. The T cell epitope-specific immune response to IC41 was assessed using [(3)H]-thymidine CD4+ T cell proliferation, interferon-gamma (IFN-gamma) CD8+ and CD4+ ELIspot and HLA-A*0201 fluorescence-activated cell sorting (FACS) tetramer-binding assays.
  
  
  RESULTS
  More than 60% of vaccinees responded in the CD4+ T cell proliferation assay in all groups. An HLA-A*0201 FACS tetramer-binding assay and IFN-gamma CD8+ ELIspot class I response of more than 70% was induced in four and three groups, respectively. IC41 induced significant immunological responses in all groups with responder rates of up to 100%. Interestingly, topical imiquimod was not able to enhance immunogenicity but was associated with a lower immune response. Local injection site reactions were mostly transient. Intradermal injections caused more pronounced reactions compared to s.c., especially erythema and edema.
  
  
  CONCLUSIONS
  Compared to a previous study intensified dosing and/or i.d. injections enhanced the response rates to the vaccine IC41 in three assays measuring T cell function. Immunization with IC41 was generally safe in this study. These results justify testing IC41 in further clinical trials with HCV-infected individuals.
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: Christa
authors.initials: C
authors.lastname: Firbas
authors.forename: Thomas
authors.initials: T
authors.lastname: Boehm
authors.forename: Vera
authors.initials: V
authors.lastname: Buerger
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Schuller
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sabarth
authors.forename: Bernd
authors.initials: B
authors.lastname: Jilma
authors.forename: Christoph S
authors.initials: CS
authors.lastname: Klade
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D000634:Aminoquinolines / Q000008:administration & dosage / Q000009:adverse effects; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D006801:Humans; D000077271:Imiquimod; D007115:Immunization Schedule; D007117:Immunization, Secondary / Q000379:methods; D007271:Injections, Intradermal; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D022223:Vaccines, Subunit; D014761:Viral Hepatitis Vaccines; D007371:Interferon-gamma; D000077271:Imiquimod