title: Therapeutic DNA vaccination using in vivo electroporation followed by standard of care therapy in patients with genotype 1 chronic hepatitis C.
abstract: Clearance of infections caused by the hepatitis C virus (HCV) correlates with HCV-specific T cell function. We therefore evaluated therapeutic vaccination in 12 patients with chronic HCV infection. Eight patients also underwent a subsequent standard-of-care (SOC) therapy with pegylated interferon (IFN) and ribavirin. The phase I/IIa clinical trial was performed in treatment naive HCV genotype 1 patients, receiving four monthly vaccinations in the deltoid muscles with 167, 500, or 1,500 μg codon-optimized HCV nonstructural (NS) 3/4A-expressing DNA vaccine delivered by in vivo electroporation (EP). Enrollment was done with 2 weeks interval between patients for safety reasons. Treatment was safe and well tolerated. The vaccinations significantly improved IFN-γ-producing responses to HCV NS3 during the first 6 weeks of therapy. Five patients experienced 2-10 weeks 0.6-2.4 log10 reduction in serum HCV RNA. Six out of eight patients starting SOC therapy within 1-30 months after the last vaccine dose were cured. This first-in-man therapeutic HCV DNA vaccine study with the vaccine delivered by in vivo EP shows transient effects in patients with chronic HCV genotype 1 infection. The interesting result noted after SOC therapy suggests that therapeutic vaccination can be explored in a combination with SOC treatment.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Ola
authors.initials: O
authors.lastname: Weiland
authors.forename: Gustaf
authors.initials: G
authors.lastname: Ahlén
authors.forename: Helmut
authors.initials: H
authors.lastname: Diepolder
authors.forename: Maria-Christina
authors.initials: MC
authors.lastname: Jung
authors.forename: Sepideh
authors.initials: S
authors.lastname: Levander
authors.forename: Michael
authors.initials: M
authors.lastname: Fons
authors.forename: Iacob
authors.initials: I
authors.lastname: Mathiesen
authors.forename: Niranjan Y
authors.initials: NY
authors.lastname: Sardesai
authors.forename: Anders
authors.initials: A
authors.lastname: Vahlne
authors.forename: Lars
authors.initials: L
authors.lastname: Frelin
authors.forename: Matti
authors.initials: M
authors.lastname: Sällberg
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D018274:Electroporation; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000235:genetics / Q000628:therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D059039:Standard of Care; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; D019444:Vaccines, DNA; D014761:Viral Hepatitis Vaccines; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a