A vaccinia-based single vector construct multi-pathogen vaccine protects against both Zika and chikungunya viruses

Nat Commun. 2018 Mar 26;9(1):1230. doi: 10.1038/s41467-018-03662-6.

Abstract

Zika and chikungunya viruses have caused major epidemics and are transmitted by Aedes aegypti and/or Aedes albopictus mosquitoes. The "Sementis Copenhagen Vector" (SCV) system is a recently developed vaccinia-based, multiplication-defective, vaccine vector technology that allows manufacture in modified CHO cells. Herein we describe a single-vector construct SCV vaccine that encodes the structural polyprotein cassettes of both Zika and chikungunya viruses from different loci. A single vaccination of mice induces neutralizing antibodies to both viruses in wild-type and IFNAR-/- mice and protects against (i) chikungunya virus viremia and arthritis in wild-type mice, (ii) Zika virus viremia and fetal/placental infection in female IFNAR-/- mice, and (iii) Zika virus viremia and testes infection and pathology in male IFNAR-/- mice. To our knowledge this represents the first single-vector construct, multi-pathogen vaccine encoding large polyproteins, and offers both simplified manufacturing and formulation, and reduced "shot burden" for these often co-circulating arboviruses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / biosynthesis
  • CHO Cells
  • Chikungunya Fever / immunology
  • Chikungunya Fever / prevention & control*
  • Chikungunya virus / immunology*
  • Chlorocebus aethiops
  • Cricetulus
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Genetic Vectors*
  • HeLa Cells
  • Humans
  • Male
  • Maternal-Fetal Exchange
  • Mice, Inbred C57BL
  • Pregnancy
  • Receptor, Interferon alpha-beta / genetics
  • Vaccinia virus / genetics*
  • Vero Cells
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / genetics*
  • Viral Vaccines / immunology*
  • Zika Virus / immunology*
  • Zika Virus Infection / immunology
  • Zika Virus Infection / prevention & control*

Substances

  • Antibodies, Neutralizing
  • Ifnar1 protein, mouse
  • Viral Vaccines
  • Receptor, Interferon alpha-beta