Impact of prior flavivirus immunity on Zika virus infection in rhesus macaques

PLoS Pathog. 2017 Aug 3;13(8):e1006487. doi: 10.1371/journal.ppat.1006487. eCollection 2017 Aug.


Studies have demonstrated cross-reactivity of anti-dengue virus (DENV) antibodies in human sera against Zika virus (ZIKV), promoting increased ZIKV infection in vitro. However, the correlation between in vitro and in vivo findings is not well characterized. Thus, we evaluated the impact of heterotypic flavivirus immunity on ZIKV titers in biofluids of rhesus macaques. Animals previously infected (≥420 days) with DENV2, DENV4, or yellow fever virus were compared to flavivirus-naïve animals following infection with a Brazilian ZIKV strain. Sera from DENV-immune macaques demonstrated cross-reactivity with ZIKV by antibody-binding and neutralization assays prior to ZIKV infection, and promoted increased ZIKV infection in cell culture assays. Despite these findings, no significant differences between flavivirus-naïve and immune animals were observed in viral titers, neutralizing antibody levels, or immune cell kinetics following ZIKV infection. These results indicate that prior infection with heterologous flaviviruses neither conferred protection nor increased observed ZIKV titers in this non-human primate ZIKV infection model.

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / immunology*
  • Cross Reactions / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Flavivirus / immunology
  • Flavivirus Infections / immunology*
  • Flavivirus Infections / pathology
  • Macaca mulatta
  • Polymerase Chain Reaction
  • Zika Virus / immunology
  • Zika Virus Infection / immunology*
  • Zika Virus Infection / pathology


  • Antibodies, Neutralizing
  • Antibodies, Viral

Grant support

This study was funded by the US Army Medical Research and Material Command. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.