Maternally Acquired Zika Antibodies Enhance Dengue Disease Severity in Mice

Cell Host Microbe. 2018 Nov 14;24(5):743-750.e5. doi: 10.1016/j.chom.2018.09.015.


Antibody (Ab)-dependent enhancement can exacerbate dengue virus (DENV) infection due to cross-reactive Abs from an initial DENV infection, facilitating replication of a second DENV. Zika virus (ZIKV) emerged in DENV-endemic areas, raising questions about whether existing immunity could affect these related flaviviruses. We show that mice born with circulating maternal Abs against ZIKV develop severe disease upon DENV infection. Compared with pups of naive mothers, those born to ZIKV-immune mice lacking type I interferon receptor in myeloid cells (LysMCre+Ifnar1fl/fl) exhibit heightened disease and viremia upon DENV infection. Passive transfer of IgG isolated from mice born to ZIKV-immune mothers resulted in increased viremia in naive recipient mice. Treatment with Abs blocking inflammatory cytokine tumor necrosis factor linked to DENV disease or Abs blocking DENV entry improved survival of DENV-infected mice born to ZIKV-immune mothers. Thus, the maternal Ab response to ZIKV infection or vaccination might predispose to severe dengue disease in infants.

Keywords: Zika; antibody-dependent enhancement (ADE); dengue; maternal antibody; mouse model; viral pathogenesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology*
  • Antibody Formation
  • Antibody-Dependent Enhancement / immunology*
  • Cell Line
  • Cross Reactions / immunology
  • Culicidae
  • Cytokines / metabolism
  • Dengue / immunology*
  • Dengue Virus / immunology*
  • Dengue Virus / pathogenicity
  • Disease Models, Animal
  • Female
  • Humans
  • Immunity
  • Immunoglobulin G
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myeloid Cells
  • Receptor, Interferon alpha-beta / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Viremia
  • Virus Internalization
  • Zika Virus / immunology*
  • Zika Virus / pathogenicity
  • Zika Virus Infection / immunology*
  • Zika Virus Infection / virology


  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Cytokines
  • Immunoglobulin G
  • Tumor Necrosis Factor-alpha
  • Receptor, Interferon alpha-beta