Induction of neutralizing antibodies against four serotypes of dengue viruses by MixBiEDIII, a tetravalent dengue vaccine

PLoS One. 2014 Jan 21;9(1):e86573. doi: 10.1371/journal.pone.0086573. eCollection 2014.

Abstract

The worldwide expansion of four serotypes of dengue virus (DENV) poses great risk to global public health. Several vaccine candidates are under development. However, none is yet available for humans. In the present study, a novel strategy to produce tetravalent DENV vaccine based on envelope protein domain III (EDIII) was proposed. Tandem EDIIIs of two serotypes (type 1-2 and type 3-4) of DENV connected by a Gly-Ser linker ((Gly4Ser)3) were expressed in E. coli, respectively. Then, the two bivalent recombinant EDIIIs were equally mixed to form the tetravalent vaccine candidate MixBiEDIII, and used to immunize BALB/c mice. The results showed that specific IgG and neutralizing antibodies against all four serotypes of DENV were successfully induced in the MixBiEDIII employing Freund adjuvant immunized mice. Furthermore, in the suckling mouse model, sera from mice immunized with MixBiEDIII provided significant protection against four serotypes of DENV challenge. Our data demonstrated that MixBiEDIII, as a novel form of subunit vaccine candidates, might have the potential to be further developed as a tetravalent dengue vaccine in the near future.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / immunology
  • Antigens, Viral / immunology
  • Cells, Cultured
  • Cricetinae
  • Culicidae / immunology
  • Dengue Vaccines / immunology*
  • Dengue Virus / immunology*
  • Escherichia coli / genetics
  • Female
  • Immunization / methods
  • Immunoglobulin G / immunology
  • Mice
  • Mice, Inbred BALB C
  • Vaccines, Subunit / immunology*
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antigens, Viral
  • Dengue Vaccines
  • Immunoglobulin G
  • Vaccines, Subunit
  • Viral Envelope Proteins

Grants and funding

This work was supported by National Basic Research Plan of China (No.2012CB518904) and National Natural Science Foundation of China (No.30972613, No.31000083, No.81101243 and No.U1132002). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.