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

Cell Host Microbe. 2018 Oct 10;24(4):487-499.e5. doi: 10.1016/j.chom.2018.09.008.

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.

Keywords: Zika virus; flavivirus capsid; vaccine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • A549 Cells
  • Animals
  • Capsid Proteins / genetics
  • Capsid Proteins / immunology*
  • Cell Line
  • Chlorocebus aethiops
  • Cricetinae
  • Female
  • Humans
  • Infectious Disease Transmission, Vertical / prevention & control*
  • Male
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Pregnancy
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / immunology
  • Vero Cells
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / immunology*
  • Zika Virus / genetics
  • Zika Virus / immunology*
  • Zika Virus Infection / prevention & control*
  • Zika Virus Infection / virology

Substances

  • Capsid Proteins
  • Vaccines, Attenuated
  • Viral Vaccines