title: Oral administration of genetically modified Bifidobacterium displaying HCV-NS3 multi-epitope fusion protein could induce an HCV-NS3-specific systemic immune response in mice.
abstract: More than 170 million people worldwide are chronic HCV (Hepatitis C virus) carriers, and about 30% of them will develop progressive liver disease, such as cirrhosis and hepatocellular carcinoma. A combination of pegylated interferon-α with ribavirin, the standard treatment for HCV infection, has been effective in fewer than 50% of patients infected with HCV genotype 1. A strong T cell response against the nonstructural protein 3 (NS3) is important for recovery from acute HCV infection, and an early multi-specific CD4+ helper and CD8+ cytotoxic T cell response is critical for HCV clearance. In the present study, we successfully constructed a genetically modified Bifidobacterium longum (B. longum) displaying recombinant HCV-NS3 peptides containing some CD4 and CD8 epitopes located in the HCV-NS3 region as an oral vaccine against chronic HCV infection. The oral administration of this vaccine could induce NS3-specific immune responses in mice through intestinal mucosal immunity. Our findings suggest that this novel oral vaccine has great potential as a novel oral vaccine against chronic HCV infection.
authors.affiliation: Division of Infectious Disease Control, Department of Microbiology and Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Saki
authors.initials: S
authors.lastname: Takei
authors.affiliation: Division of Infectious Disease Control, Department of International Health, Kobe University Graduate School of Health Sciences, Kobe, Japan.
authors.forename: Chika
authors.initials: C
authors.lastname: Omoto
authors.affiliation: Division of Infectious Disease Control, Department of International Health, Kobe University Graduate School of Health Sciences, Kobe, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kitagawa
authors.affiliation: Division of Infectious Disease Control, Department of Microbiology and Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Morishita
authors.affiliation: Research Institute for Bioresources and Biotechnology, Ishikawa Prefectural University, Ishikawa, Japan.
authors.forename: Takane
authors.initials: T
authors.lastname: Katayama
authors.affiliation: Department of Surgery Related Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Shigemura
authors.affiliation: Department of Surgery Related Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Fujisawa
authors.affiliation: Division of Infectious Disease Control, Department of Microbiology and Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Japan; Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Kawabata
authors.affiliation: Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Japan; Division of Microbiology, Department of Microbiology and Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Hak
authors.initials: H
authors.lastname: Hotta
authors.affiliation: Division of Infectious Disease Control, Department of Microbiology and Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Japan; Division of Infectious Disease Control, Department of International Health, Kobe University Graduate School of Health Sciences, Kobe, Japan; Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Japan; Department of Surgery Related Urology, Kobe University Graduate School of Medicine, Kobe, Japan. Electronic address: toshiro@med.kobe-u.ac.jp.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Shirakawa
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D001644:Bifidobacterium / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006526:Hepatitis C / Q000517:prevention & control*; D018928:Immunity, Mucosal; D007422:Intestines / Q000276:immunology; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000276:immunology*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D000939:Epitopes; D011993:Recombinant Fusion Proteins; D014761:Viral Hepatitis Vaccines; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
keywords: Bifidobacterium; HCV; Mucosal vaccine; NS3