title: Bivalent vaccine platform based on Japanese encephalitis virus (JEV) elicits neutralizing antibodies against JEV and hepatitis C virus.
abstract: Directly acting antivirals recently have become available for the treatment of hepatitis C virus (HCV) infection, but there is no prophylactic vaccine for HCV. In the present study, we took advantage of the properties of Japanese encephalitis virus (JEV) to develop antigens for use in a HCV vaccine. Notably, the surface-exposed JEV envelope protein is tolerant of inserted foreign epitopes, permitting display of novel antigens. We identified 3 positions that permitted insertion of the HCV E2 neutralization epitope recognized by HCV1 antibody. JEV subviral particles (SVP) containing HCV-neutralization epitope (SVP-E2) were purified from culture supernatant by gel chromatography. Sera from mice immunized with SVP-E2 inhibited infection by JEV and by trans-complemented HCV particles (HCVtcp) derived from multi-genotypic viruses, whereas sera from mice immunized with synthetic E2 peptides did not show any neutralizing activity. Furthermore, sera from mice immunized with SVP-E2 neutralized HCVtcp with N415K escape mutation in E2. As with the SVP-E2 epitope-displaying particles, JEV SVPs with HCV E1 epitope also elicited neutralizing antibodies against HCV. Thus, this novel platform harboring foreign epitopes on the surface of the particle may facilitate the development of a bivalent vaccine against JEV and other pathogens.
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.|Department of Life Science and Medical Bioscience, Waseda University, 2-2, Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Ryohei
authors.initials: R
authors.lastname: Saga
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Fujimoto
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Watanabe
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Mami
authors.initials: M
authors.lastname: Matsuda
authors.affiliation: Department of Bioscience, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura-cho, Nagahama-shi, Shiga 526-0829, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Hasegawa
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Watashi
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Aizaki
authors.affiliation: Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1, Tebiro, kanagawa-shi, Kanagawa 248-0036, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Nakamura
authors.affiliation: Department of Virology I, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tajima
authors.affiliation: Department of Virology I, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Takasaki
authors.affiliation: BIKEN Endowed Department of Dengue Vaccine Development Faculty of Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Ratchahewi, Bangkok 10440, Thailand.|BIKEN Endowed Department of Dengue Vaccine Development, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Konishi
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Kato
authors.affiliation: Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
authors.forename: Michinori
authors.initials: M
authors.lastname: Kohara
authors.affiliation: Department of Life Science and Medical Bioscience, Waseda University, 2-2, Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Haruko
authors.initials: H
authors.lastname: Takeyama
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Takaji
authors.initials: T
authors.lastname: Wakita
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004664:Encephalitis Virus, Japanese / Q000235:genetics / Q000276:immunology*; D004672:Encephalitis, Japanese / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006526:Hepatitis C / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D018937:Hepatitis C Antibodies / Q000276:immunology; D022301:Herpes Simplex Virus Vaccines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D006801:Humans; D022321:Japanese Encephalitis Vaccines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D018937:Hepatitis C Antibodies; D022301:Herpes Simplex Virus Vaccines; D022321:Japanese Encephalitis Vaccines