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

Microbiol Immunol. 2014 Feb;58(2):126-34. doi: 10.1111/1348-0421.12125.

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.

Keywords: Antibody-dependent enhancement; chimera; dengue; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology
  • CHO Cells
  • Cell Line
  • Cricetulus
  • Dengue / immunology*
  • Dengue Vaccines / genetics
  • Dengue Vaccines / immunology*
  • Dengue Virus / classification
  • Dengue Virus / genetics
  • Dengue Virus / immunology*
  • Encephalitis Viruses, Japanese / classification
  • Encephalitis Viruses, Japanese / genetics
  • Encephalitis Viruses, Japanese / immunology*
  • Gene Expression
  • Humans
  • Immunization
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Male
  • Mice
  • Neutralization Tests
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Serotyping
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology*
  • Viral Envelope Proteins / chemistry
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antigens, Viral
  • Dengue Vaccines
  • Immunoglobulin G
  • Recombinant Fusion Proteins
  • Vaccines, DNA
  • Viral Envelope Proteins