Vaccine-induced protection of rhesus macaques against plasma viremia after intradermal infection with a European lineage 1 strain of West Nile virus

PLoS One. 2014 Nov 13;9(11):e112568. doi: 10.1371/journal.pone.0112568. eCollection 2014.

Abstract

The mosquito-borne West Nile virus (WNV) causes human and animal disease with outbreaks in several parts of the world including North America, the Mediterranean countries, Central and East Europe, the Middle East, and Africa. Particularly in elderly people and individuals with an impaired immune system, infection with WNV can progress into a serious neuroinvasive disease. Currently, no treatment or vaccine is available to protect humans against infection or disease. The goal of this study was to develop a WNV-vaccine that is safe to use in these high-risk human target populations. We performed a vaccine efficacy study in non-human primates using the contemporary, pathogenic European WNV genotype 1a challenge strain, WNV-Ita09. Two vaccine strategies were evaluated in rhesus macaques (Macaca mulatta) using recombinant soluble WNV envelope (E) ectodomain adjuvanted with Matrix-M, either with or without DNA priming. The DNA priming immunization was performed with WNV-DermaVir nanoparticles. Both vaccination strategies successfully induced humoral and cellular immune responses that completely protected the macaques against the development of viremia. In addition, the vaccine was well tolerated by all animals. Overall, The WNV E protein adjuvanted with Matrix-M is a promising vaccine candidate for a non-infectious WNV vaccine for use in humans, including at-risk populations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / blood
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Culicidae
  • Europe
  • Immunity, Cellular
  • Immunity, Humoral
  • Injections, Intradermal
  • Interferon-gamma / immunology
  • Macaca mulatta
  • Protein Structure, Tertiary
  • Viral Envelope Proteins / immunology
  • Viral Load
  • Viremia / immunology
  • West Nile Fever / prevention & control*
  • West Nile Virus Vaccines / therapeutic use*
  • West Nile virus / classification*

Substances

  • Antibodies, Viral
  • Viral Envelope Proteins
  • West Nile Virus Vaccines
  • Interferon-gamma

Grant support

The project was funded by the European Community FP7 project WINGS (grant no. 261426). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.