Abstract

We previously demonstrated that a DNA-based tetravalent dengue vaccine can induce balanced neutralizing antibody responses against all four types of dengue virus (DENV1–4), using naive mice. On the other hand, individuals receiving the dengue vaccine may have previously been infected with dengue virus (DENV1–4) or vaccinated with other fl avivirus vaccines. Thus, we investigated the effect of preimmunity against fl aviviruses on immunogenicity of a dengue tetravalent DNA vaccine in mice. Mice preimmunized with DENV2 developed higher antibody levels against DENV2 than other types of dengue virus after the fi rst dengue vaccination. However, the second vaccination provided similar increases (4- to 8-fold) in antibody levels against all types of dengue virus, compared with non-preimmunized mice. Preimmunization with yellow fever or Japanese encephalitis vaccines did not affect the immunogenicity of the tetravalent vaccine, except for slight and occasional increases in antibody levels against certain types of viruses. Thus, the dengue tetravalent DNA vaccine could provide balanced induction of dengue antibody responses even in mice preimmunized with any of the three fl aviviruses, at least after the second vaccination.

Highlights

  • Dengue fever (DF) is a mosquito-borne viral disease widely distributed in most tropical and subtropical regions [7,12]

  • Since this study aimed to investigate immunogenicity of the dengue tetravalent DNA vaccine in mice with preimmunity to antigens of DENV2, JE virus (JEV) or YF virus (YFV), we evaluated cross-neutralization among these viruses

  • This study assessed the effects of preimmunity to DENV2, JEVAX and YFV on immunogenicity of the dengue tetravalent DNA vaccine in mice

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Summary

Introduction

Dengue fever (DF) is a mosquito-borne viral disease widely distributed in most tropical and subtropical regions [7,12]. An estimated 50–100 million human cases occur annually. One of the important features of this disease is the presence of its severe form, dengue hemorrhagic fever (DHF). 250,000–500,000 cases of DHF have been reported every year. The causative agent of DF and DHF is any of four types of dengue virus (dengue type 1–4 virus; designated DENV1–4), members of the genus Flavivirus in the family Flaviviridae [25]. There are currently no approved vaccines and no specific antiviral drugs available against the dengue virus [14,33]

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