Impact of prior Dengue immunity on Zika vaccine protection in rhesus macaques and mice

PLoS Pathog. 2021 Jun 25;17(6):e1009673. doi: 10.1371/journal.ppat.1009673. eCollection 2021 Jun.


Pre-existing immunity to flaviviruses can influence the outcome of subsequent flavivirus infections. Therefore, it is critical to determine whether baseline DENV immunity may influence subsequent ZIKV infection and the protective efficacy of ZIKV vaccines. In this study, we investigated the impact of pre-existing DENV immunity induced by vaccination on ZIKV infection and the protective efficacy of an inactivated ZIKV vaccine. Rhesus macaques and mice inoculated with a live attenuated DENV vaccine developed neutralizing antibodies (NAbs) to multiple DENV serotypes but no cross-reactive NAbs responses to ZIKV. Animals with baseline DENV NAbs did not exhibit enhanced ZIKV infection and showed no overall reduction in ZIKV vaccine protection. Moreover, passive transfer of purified DENV-specific IgG from convalescent human donors did not augment ZIKV infection in STAT2 -/- and BALB/c mice. In summary, these results suggest that baseline DENV immunity induced by vaccination does not significantly enhance ZIKV infection or impair the protective efficacy of candidate ZIKV vaccines in these models. These data can help inform immunization strategies in regions of the world with multiple circulating pathogenic flaviviruses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology*
  • Cross Reactions / immunology
  • Dengue Vaccines / immunology*
  • Humans
  • Macaca mulatta
  • Mice
  • Viral Vaccines / immunology
  • Zika Virus Infection / prevention & control*


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Dengue Vaccines
  • Viral Vaccines

Grants and funding

Henry M. Jackson Foundation (W81XWH-11-2-0174) and the Ragon Institute of MGH, MIT, and Harvard (DHB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.