A Single-Dose Live-Attenuated Zika Virus Vaccine with Controlled Infection Rounds that Protects against Vertical Transmission

Xuping Xie, Dieudonné B. Kum, Hongjie Xia, Huanle Luo, Chao Shan, Jing Zou, Antonio E. Muruato, Daniele B.A. Medeiros, Bruno T.D. Nunes, Kai Dallmeier, Shannan L. Rossi, Scott C. Weaver, Johan Neyts, Tian Wang, Pedro F.C. Vasconcelos, Pei Yong Shi

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Zika virus (ZIKV) infection of the mother during pregnancy causes devastating Zika congenital syndrome in the offspring. A ZIKV vaccine with optimal safety and immunogenicity for use in pregnant women is critically needed. Toward this goal, we have developed a single-dose live-attenuated vaccine candidate that infects cells with controlled, limited infection rounds. The vaccine contains a 9-amino-acid deletion in the viral capsid protein and replicates to titers of > 106 focus-forming units (FFU)/mL in cells expressing the full-length capsid protein. Immunization of A129 mice with one dose (105 FFU) did not produce viremia, but elicited protective immunity that completely prevented viremia, morbidity, and mortality after challenge with an epidemic ZIKV strain (106 PFU). A single-dose vaccination also fully prevented infection of pregnant mice and maternal-to-fetal transmission. Intracranial injection of the vaccine (104 FFU) to 1-day-old mice did not cause any disease or death, underscoring the safety of this vaccine candidate. A ZIKV vaccine for use in pregnant women requires an optimal balance between safety and immunogenicity. Xie et al. developed a live-attenuated vaccine candidate that can infect cells with controlled, limited infection rounds. A single-dose immunization of the vaccine prevents vertical transmission of ZIKV in pregnant mice.

Original languageEnglish (US)
Pages (from-to)487-499.e5
JournalCell Host and Microbe
Volume24
Issue number4
DOIs
StatePublished - Oct 10 2018

Keywords

  • Zika virus
  • flavivirus capsid
  • vaccine

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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