Recombinant vesicular stomatitis virus-based west Nile vaccine elicits strong humoral and cellular immune responses and protects mice against lethal challenge with the virulent west Nile virus strain LSU-AR01

Vaccine. 2009 Feb 5;27(6):893-903. doi: 10.1016/j.vaccine.2008.11.087. Epub 2008 Dec 12.

Abstract

Vesicular stomatitis virus (VSV) has been extensively utilized as a viral vector system for the induction of protective immune responses against a variety of pathogens. We constructed recombinant VSVs specifying either the Indiana or Chandipura virus G glycoprotein and expressing the West Nile virus (WNV) envelope (E) glycoprotein. Mice were intranasally vaccinated using a prime (Indiana)-boost (Chandipura) immunization approach and challenged with the virulent WNV-LSU-AR01. Ninety-percent (9 of 10) of the vaccinated mice survived as compared to 10% of the mock-vaccinated mice after WNV lethal challenge. Histopathological examination of brain tissues revealed neuronal necrosis in mock-vaccinated mice but not in vaccinated mice, and vaccinated, but not mock-vaccinated mice developed a strong neutralizing antibody response against WNV. Extensive immunological analysis using polychromatic flow cytometry staining revealed that vaccinated, but not mock-vaccinated mice developed robust cellular immune responses as evidenced by up-regulation of CD4(+) CD154(+) IFNgamma(+) T cells in vaccinated, but not mock-vaccinated mice. Similarly, vaccinated mice developed robust E-glycoprotein-specific CD8(+) T cell immune responses as evidenced by the presence of a high percentage of CD8(+) CD62L(low) IFNgamma(+) cells. In addition, a sizeable population of CD8(+) CD69(+) cells was detected indicating E-specific activation of mature T cells and CD4(+) CD25(+) CD127(low) T regulatory (T reg) cells were down-regulated. These results suggest that VSV-vectored vaccines administered intranasally can efficiently induce protective humoral and cellular immune responses against WNV infections.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Viral / blood*
  • Brain / pathology
  • Cricetinae
  • Female
  • Interferon-gamma / biosynthesis
  • Lymphocyte Subsets / immunology
  • Mice
  • Mice, Inbred BALB C
  • Neutralization Tests
  • Survival Analysis
  • T-Lymphocytes / immunology*
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology
  • Vesicular stomatitis Indiana virus / genetics
  • Vesicular stomatitis Indiana virus / immunology*
  • Vesiculovirus / genetics
  • Vesiculovirus / immunology*
  • Viral Structural Proteins / genetics
  • Viral Structural Proteins / immunology*
  • West Nile Fever / prevention & control
  • West Nile Virus Vaccines / genetics
  • West Nile Virus Vaccines / immunology*

Substances

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