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A systematic approach to the development of a safe live attenuated Zika vaccine.

Swee Sen KwekSatoru WatanabeKuan Rong ChanEugenia Z OngHwee Cheng TanWy Ching NgMien T X NguyenEsther S GanSummer L ZhangKitti Wing Ki ChanJun Hao TanOctober M SessionsMenchie ManuelJulien PomponCamillus Jian Hui ChuaSharifah HazirahKarl TryggvasonSubhash G VasudevanEng Eong Ooi
Published in: Nature communications (2018)
Zika virus (ZIKV) is a flavivirus that can cause congenital disease and requires development of an effective long-term preventative strategy. A replicative ZIKV vaccine with properties similar to the yellow fever 17D (YF17D) live-attenuated vaccine (LAV) would be advantageous, as a single dose of YF17D produces lifelong immunity. However, a replicative ZIKV vaccine must also be safe from causing persistent organ infections. Here we report an approach to ZIKV LAV development. We identify a ZIKV variant that produces small plaques due to interferon (IFN)-restricted viral propagation and displays attenuated infection of endothelial cells. We show that these properties collectively reduce the risk of organ infections and vertical transmission in a mouse model but remain sufficiently immunogenic to prevent wild-type ZIKV infection. Our findings suggest a strategy for the development of a safe but efficacious ZIKV LAV.
Keyphrases
  • zika virus
  • dengue virus
  • aedes aegypti
  • endothelial cells
  • mouse model
  • dendritic cells
  • sars cov
  • immune response
  • vascular endothelial growth factor