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.
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.
Iyer
Arun V
AV
Louisiana State University School of Veterinary Medicine, Baton Rouge, LA 70803, USA.
Pahar
Bapi
B
Boudreaux
Marc J
MJ
Wakamatsu
Nobuko
N
Roy
Alma F
AF
Chouljenko
Vladimir N
VN
Baghian
Abolghasem
A
Apetrei
Cristian
C
Marx
Preston A
PA
Kousoulas
Konstantin G
KG
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D001921:Brain / Q000473:pathology; D006224:Cricetinae; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D016131:Lymphocyte Subsets / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000276:immunology*; D018116:Vesiculovirus / Q000235:genetics / Q000276:immunology*; D015678:Viral Structural Proteins / Q000235:genetics / Q000276:immunology*; D014901:West Nile Fever / Q000517:prevention & control; D053060:West Nile Virus Vaccines / Q000235:genetics / Q000276:immunology*
D000914:Antibodies, Viral; D014614:Vaccines, Synthetic; D015678:Viral Structural Proteins; D053060:West Nile Virus Vaccines; D007371:Interferon-gamma