Protection of a single dose west nile virus recombinant subviral particle vaccine against lineage 1 or 2 strains and analysis of the cross-reactivity with Usutu virus

PLoS One. 2014 Sep 17;9(9):e108056. doi: 10.1371/journal.pone.0108056. eCollection 2014.

Abstract

West Nile virus (WNV) is a neurovirulent mosquito-borne flavivirus. High WNV virulence was mainly associated with lineage 1 strains, but recent outbreaks have unveiled circulation of highly virulent lineage 2 strains. Co-expression of flavivirus prM and E glycoproteins drives the assembly of recombinant subviral particles (RSPs) that share antigenic features with virions. Mouse immunization with lineage 1 WNV RSPs induced a potent humoral response against WNV with production of neutralizing antibodies. A single inoculation of RSPs formulated with Al(OH)3 as adjuvant protected mice against a lethal challenge with WNV strains from lineage 1 or 2. The cross-reactivity of the response elicited by these RSPs was analyzed against the related flavivirus Usutu virus (USUV), which shares multiple ecological and antigenic features with WNV. Immunization with WNV-RSPs increased specific, although low, antibody titers found upon subsequent USUV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Viral / immunology
  • Cross Reactions*
  • Female
  • Genetic Variation
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Immunity, Humoral
  • Immunization
  • Mice
  • Vaccines, Synthetic / immunology
  • Viral Envelope Proteins / immunology
  • West Nile Virus Vaccines / immunology*
  • West Nile virus / genetics
  • West Nile virus / immunology*

Substances

  • Antigens, Viral
  • Vaccines, Synthetic
  • Viral Envelope Proteins
  • West Nile Virus Vaccines

Grants and funding

This work was supported by grant BIO2011-24351 and an institutional grant from Fundación Ramón Areces to F.S., grant RTA2013-0036 to J.-C.S. and by grant ERTA2013-00013-C04-00. M.A.M.-A. is a recipient of a “Junta de Ampliación de Estudios (JAE)”? post-doctoral fellowship from the Spanish Research Council (CSIC). T.M.-R. is a recipient of a “Formación de Personal Investigador (FPI)”? pre-doctoral fellowship from INIA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.