Bivalent vaccine platform based on Japanese encephalitis virus (JEV) elicits neutralizing antibodies against JEV and hepatitis C virus

Ryohei Saga, Akira Fujimoto, Noriyuki Watanabe, Mami Matsuda, Makoto Hasegawa, Koichi Watashi, Hideki Aizaki, Noriko Nakamura, Shigeru Tajima, Tomohiko Takasaki, Eiji Konishi, Takanobu Kato, Michinori Kohara, Haruko Takeyama, Takaji Wakita, Ryosuke Suzuki

    Research output: Contribution to journalArticle

    3 Citations (Scopus)

    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.

    Original languageEnglish
    Article number28688
    JournalScientific Reports
    Volume6
    DOIs
    Publication statusPublished - 2016 Jun 27

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    Japanese Encephalitis Virus
    Neutralizing Antibodies
    Hepacivirus
    Vaccines
    Epitopes
    Serum
    Antigens
    Virus Diseases
    Virion
    Antiviral Agents
    Gel Chromatography

    ASJC Scopus subject areas

    • General

    Cite this

    Bivalent vaccine platform based on Japanese encephalitis virus (JEV) elicits neutralizing antibodies against JEV and hepatitis C virus. / Saga, Ryohei; Fujimoto, Akira; Watanabe, Noriyuki; Matsuda, Mami; Hasegawa, Makoto; Watashi, Koichi; Aizaki, Hideki; Nakamura, Noriko; Tajima, Shigeru; Takasaki, Tomohiko; Konishi, Eiji; Kato, Takanobu; Kohara, Michinori; Takeyama, Haruko; Wakita, Takaji; Suzuki, Ryosuke.

    In: Scientific Reports, Vol. 6, 28688, 27.06.2016.

    Research output: Contribution to journalArticle

    Saga, R, Fujimoto, A, Watanabe, N, Matsuda, M, Hasegawa, M, Watashi, K, Aizaki, H, Nakamura, N, Tajima, S, Takasaki, T, Konishi, E, Kato, T, Kohara, M, Takeyama, H, Wakita, T & Suzuki, R 2016, 'Bivalent vaccine platform based on Japanese encephalitis virus (JEV) elicits neutralizing antibodies against JEV and hepatitis C virus', Scientific Reports, vol. 6, 28688. https://doi.org/10.1038/srep28688
    Saga, Ryohei ; Fujimoto, Akira ; Watanabe, Noriyuki ; Matsuda, Mami ; Hasegawa, Makoto ; Watashi, Koichi ; Aizaki, Hideki ; Nakamura, Noriko ; Tajima, Shigeru ; Takasaki, Tomohiko ; Konishi, Eiji ; Kato, Takanobu ; Kohara, Michinori ; Takeyama, Haruko ; Wakita, Takaji ; Suzuki, Ryosuke. / Bivalent vaccine platform based on Japanese encephalitis virus (JEV) elicits neutralizing antibodies against JEV and hepatitis C virus. In: Scientific Reports. 2016 ; Vol. 6.
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    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.",
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