Focused dengue vaccine development: outwitting nature's design

Pathog Dis. 2019 Feb 1;77(1):ftz003. doi: 10.1093/femspd/ftz003.


The four DENV serotypes are mosquito-borne pathogens that belong to the Flavivirus genus. These viruses present a major global health burden, being endemic in over 120 countries, causing ∼390 million reported infections yearly, with clinical symptoms ranging from mild fever to severe and potentially fatal hemorrhagic syndromes. Development of a safe and efficacious DENV vaccine is challenging because of the need to induce immunity against all four serotypes simultaneously, as immunity against one serotype can potentially enhance disease caused by a heterotypic secondary infection. So far, live-virus particle-based vaccine approaches struggle with inducing protective tetravalent immunity, while recombinant subunit approaches that use the envelope protein (E) as the major antigen, are gaining promise in preclinical studies. However, E-based subunits require further development and characterization to be used as effective vaccine antigens against DENV. In this review, we will address the shortcomings of recombinant E-based antigens and will discuss potential solutions to enhance E-based subunit antigen immunogenicity and vaccine efficacy.

Keywords: dengue virus; dimer; envelope protein; quaternary epitopes; subunit vaccine; virology.

Publication types

  • Review

MeSH terms

  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • Antigens, Viral / chemistry
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology
  • Bioengineering
  • Dengue / immunology*
  • Dengue / prevention & control
  • Dengue Vaccines / immunology*
  • Dengue Virus / immunology*
  • Humans
  • Research*
  • Vaccines, Subunit / immunology
  • Viral Envelope Proteins / chemistry
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology


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