Evaluation of chimeric DNA vaccines consisting of premembrane and envelope genes of Japanese encephalitis and dengue viruses as a strategy for reducing induction of dengue virus infection-enhancing antibody response

Authors

  • Fithriyah Sjatha,

    1. Department of Vaccinology, Center for Infectious Diseases, Kobe University Graduate School of Medicine
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  • Miwa Kuwahara,

    1. Department of International Health, Kobe University Graduate School of Health Sciences, Kobe, Japan
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  • T. Mirawati Sudiro,

  • Masanori Kameoka,

    1. Department of Vaccinology, Center for Infectious Diseases, Kobe University Graduate School of Medicine
    2. Department of International Health, Kobe University Graduate School of Health Sciences, Kobe, Japan
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  • Eiji Konishi

    Corresponding author
    1. Department of Vaccinology, Center for Infectious Diseases, Kobe University Graduate School of Medicine
    2. BIKEN Endowed Department of Dengue Vaccine Development, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
    • Correspondence

      Fithriyah Sjatha, Department of Vaccinology, Center for Infectious Diseases, Graduate School of Medicine, Kobe University, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. Tel.: +81 78 382 5502; fax: +81 78 382 5519;

      email: titi_sjatha@yahoo.com

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ABSTRACT

Neutralizing antibodies induced by dengue virus (DENV) infection show viral infection-enhancing activities at sub-neutralizing doses. On the other hand, preimmunity against Japanese encephalitis virus (JEV), a congener of DENV, does not increase the severity of DENV infection. Several studies have demonstrated that neutralizing epitopes in the genus Flavivirus are mainly located in domain III (DIII) of the envelope (E) protein. In this study, chimeric premembrane and envelope (prM-E) gene-based expression plasmids of JEV and DENV1 with DIII substitution of each virus were constructed for use as DNA vaccines and their immunogenicity evaluated. Sera from C3H/He and ICR mice immunized with a chimeric gene containing DENV1 DIII on a JEV prM-E gene backbone showed high neutralizing antibody titers with less DENV infection-enhancing activity. Our results confirm the applicability of this approach as a new dengue vaccine development strategy.

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