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

Abstract
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.
AuthorsRafael A Larocca, Peter Abbink, John D Ventura, Abishek Chandrashekar, Noe Mercado, Zhenfeng Li, Erica Borducchi, Rafael A De La Barrera, Kenneth H Eckels, Kayvon Modjarrad, Michael P Busch, Nelson L Michael, Dan H Barouch
JournalPLoS pathogens (PLoS Pathog) Vol. 17 Issue 6 Pg. e1009673 (06 2021) ISSN: 1553-7374 [Electronic] United States
PMID34170962 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Dengue Vaccines
  • Viral Vaccines
Topics
  • Animals
  • Antibodies, Neutralizing (blood, immunology)
  • Antibodies, Viral (blood, immunology)
  • Cross Reactions (immunology)
  • Dengue Vaccines (immunology)
  • Humans
  • Macaca mulatta
  • Mice
  • Viral Vaccines (immunology)
  • Zika Virus Infection (prevention & control)

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