The relative contribution of antibody and CD8+ T cells to vaccine immunity against West Nile encephalitis virus.
West Nile virus (WNV) is a mosquito borne, neurotropic flavivirus that causes a severe central nervous system (CNS) infection in humans and animals. Although commercial vaccines are available for horses, none is currently approved for human use. In this study, we evaluated the efficacy and mechanism of immune protection of two candidate WNV vaccines in mice. A formalin-inactivated WNV vaccine induced higher levels of specific and neutralizing antibodies compared to a DNA plasmid vaccine that produces virus-like particles. Accordingly, partial and almost complete protection against a highly stringent lethal intracranial WNV challenge were observed in mice 60 days after single dose immunization with the DNA plasmid and inactivated virus vaccines, respectively. In mice immunized with a single dose of DNA plasmid or inactivated vaccine, antigen-specific CD8(+) T cells were induced and contributed to protective immunity as acquired or genetic deficiencies of CD8(+) T cells lowered the survival rates. In contrast, in boosted animals, WNV-specific antibody titers were higher, survival rates after challenge were greater, and an absence of CD8(+) T cells did not appreciably affect mortality. Overall, our experiments suggest that in mice, both inactivated WNV and DNA plasmid vaccines are protective after two doses, and the specific contribution of antibody and CD8(+) T cells to vaccine immunity against WNV is modulated by the prime-boost strategy.
Shrestha
Bimmi
B
Department of Medicine, 660 S. Euclid Avenue, Box 8051, Washington University School of Medicine, St. Louis, MO 63110, United States.
Ng
Terry
T
Chu
Hsien-Jue
HJ
Noll
Michelle
M
Diamond
Michael S
MS
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D000918:Antibody Specificity; D016827:CD8 Antigens / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D007117:Immunization, Secondary; D007273:Injections, Intramuscular; D007274:Injections, Intraperitoneal; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D010957:Plasmids; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D014901:West Nile Fever / Q000097:blood / Q000276:immunology* / Q000517:prevention & control*; D014902:West Nile virus / Q000276:immunology*
D000914:Antibodies, Viral; D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D019444:Vaccines, DNA; D014765:Viral Vaccines