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

Autor: Vladimir N. Chouljenko, Preston A. Marx, Cristian Apetrei, Alma Roy, Arun V. Iyer, Nobuko Wakamatsu, Abolghasem Baghian, Marc J. Boudreaux, Bapi Pahar, Konstantin G. Kousoulas
Rok vydání: 2009
Předmět:
T-Lymphocytes
viruses
Antibodies
Viral
Recombinant virus
Mice
Cricetinae
West Nile Virus Vaccines
Mice
Inbred BALB C
Vaccines
Synthetic
0303 health sciences
Brain
3. Good health
Flavivirus
Infectious Diseases
medicine.anatomical_structure
Vesicular stomatitis virus
Molecular Medicine
Female
Antibody
West Nile virus
T cell
chemical and pharmacologic phenomena
Mucosal immunization
Biology
Article
Vesicular stomatitis Indiana virus
Virus
Microbiology
Humoral and cellular immunity
Interferon-gamma
03 medical and health sciences
Viral vector
Immune system
Neutralization Tests
medicine
Animals
030304 developmental biology
Viral Structural Proteins
General Veterinary
General Immunology and Microbiology
030306 microbiology
Public Health
Environmental and Occupational Health
Vesiculovirus
biology.organism_classification
Survival Analysis
Virology
Lymphocyte Subsets
Humoral immunity
biology.protein
West Nile Fever
Zdroj: Vaccine
ISSN: 0264-410X
DOI: 10.1016/j.vaccine.2008.11.087
Popis: 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.
Databáze: OpenAIRE
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