Dengue Virus and Zika Virus Serological Cross-reactivity and Their Impact on Pathogenesis in Mice

J Infect Dis. 2019 Jan 7;219(2):223-233. doi: 10.1093/infdis/jiy482.

Abstract

Preexisting immunity to Zika virus (ZIKV) or dengue virus (DENV) may alter the course of their infection, and here we use robust mouse models to examine pathological outcomes following passive immunization, sequential cross-infection, or vaccination with inactivated virus. DENV infection was enhanced (through antibody-dependent enhancement [ADE]) or was suppressed by both DENV and ZIKV immunity. Notably, inactivated ZIKV vaccination enhanced dengue disease severity, although it was highly protective against ZIKV infection. On the other hand, ADE was not observed upon ZIKV infection in mice that were passively immunized or preinfected with DENV. Surprisingly, however, we found that vaccination with inactivated DENV enhanced ZIKV infection, mainly in the mesenteric lymph node, indicating the potential for DENV immunity to cause ADE in vivo. Collectively, our data call for greater attention to detail in the design of ZIKV or DENV vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Antibody-Dependent Enhancement / immunology
  • Cell Line
  • Cross Reactions / immunology*
  • Dengue / blood
  • Dengue / immunology*
  • Dengue / pathology
  • Dengue Vaccines
  • Dengue Virus / genetics
  • Dengue Virus / immunology*
  • Dengue Virus / pathogenicity*
  • Disease Models, Animal
  • Genome, Viral
  • Humans
  • Immunity
  • Immunization
  • Lymph Nodes
  • Mice
  • THP-1 Cells
  • Vaccination
  • Virus Inactivation
  • Zika Virus / genetics
  • Zika Virus / immunology*
  • Zika Virus / pathogenicity*
  • Zika Virus Infection / blood
  • Zika Virus Infection / immunology*
  • Zika Virus Infection / pathology

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Dengue Vaccines