Enhanced effect of modified Zika virus E antigen on the immunogenicity of DNA vaccine

Virology. 2020 Oct:549:25-31. doi: 10.1016/j.virol.2020.07.014. Epub 2020 Jul 30.

Abstract

It has been reported worldwide that the Zika virus (ZIKV) could be transmitted through placentas and sexual contact. ZIKV can also cause Guillain-Barre syndrome, microcephaly and neurological abnormalities. However, there are no approved vaccines available. We constructed six DNA vaccine candidates and tested the immunogenicity. Tandem repeated envelope domain Ⅲ (ED Ⅲ × 3) induced highly total IgG and neutralization antibody, as well as CD8+ T cell responses. Also, stem region-removed envelope (E ΔSTEM) elicited a robust production of IFN-γ in mice. To examine in vivo protection, we used mice treated with an IFNAR1 blocking antibody before and after the challenge. Vaccination with the two candidates led to a decline in the level of viral RNAs in organs. Moreover, the sera from the vaccinated mice did not enhance the infection of Dengue virus in K562 cells. These findings suggest the potential for the development of a novel ZIKV DNA vaccine.

Keywords: DNA vaccine; Envelope protein; Immunogenicity; Mouse challenge; Zika virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / biosynthesis*
  • Antibodies, Viral / biosynthesis*
  • Antigens, Viral / chemistry
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology
  • Chlorocebus aethiops
  • Dengue Virus / drug effects
  • Dengue Virus / growth & development
  • Disease Models, Animal
  • Female
  • HEK293 Cells
  • Humans
  • Immunogenicity, Vaccine
  • K562 Cells
  • Mice
  • Receptor, Interferon alpha-beta / antagonists & inhibitors
  • Receptor, Interferon alpha-beta / genetics
  • Receptor, Interferon alpha-beta / immunology
  • Vaccination / methods
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / biosynthesis*
  • Vaccines, DNA / genetics
  • Vero Cells
  • Viral Envelope Proteins / chemistry
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology*
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / biosynthesis*
  • Viral Vaccines / genetics
  • Zika Virus / drug effects*
  • Zika Virus / genetics
  • Zika Virus / immunology
  • Zika Virus Infection / immunology
  • Zika Virus Infection / prevention & control*
  • Zika Virus Infection / virology

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antigens, Viral
  • Ifnar1 protein, mouse
  • Vaccines, DNA
  • Viral Envelope Proteins
  • Viral Vaccines
  • Receptor, Interferon alpha-beta