Development and characterization of non-glycosylated E and NS1 mutant viruses as a potential candidate vaccine for West Nile virus.
West Nile virus is an arthropod-borne flavivirus that has caused substantial morbidity and mortality to animals as well as humans since its introduction in to the New York area in 1999. Given that there are no antiviral drugs available for treatment of the disease, vaccines provide an efficacious alternative to control this disease. Herein we describe an attenuated WNV strain developed by the ablation of the glycosylation sites in the envelope (E) and non-structural 1 (NS1) proteins. This E(154S)/NS1(130A/175A/207A) strain showed modest reduction in multiplication kinetics in cell culture and small plaque phenotype compared to the parental NY99 strain yet displayed greater than a 200,000-fold attenuation for mouse neuroinvasiveness compared to the parental strain. Mice infected with 1000PFU of E(154S)/NS1(130A/175A/207A) showed undectable viremia at either two or three days post infection; nonetheless, high titer neutralizing antibodies were detected in mice inoculated with low doses of this virus and protected against lethal challenge with a 50% protective dose of 50PFU.
Whiteman
Melissa C
MC
Sealy Center for Vaccine Development, Center for Biodefense and Emerging Infectious Diseases, Institute for Human Infections, Immunity and Department of Pathology, TX 77555-0609, USA.
Li
Li
L
Wicker
Jason A
JA
Kinney
Richard M
RM
Huang
Claire
C
Beasley
David W C
DW
Chung
Kyung Min
KM
Diamond
Michael S
MS
Solomon
Tom
T
Barrett
Alan D T
AD
D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D006031:Glycosylation; D051379:Mice; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000378:metabolism*; D010948:Viral Plaque Assay; D014766:Viremia; D014774:Virulence; D014901:West Nile Fever / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D053060:West Nile Virus Vaccines / Q000235:genetics* / Q000276:immunology*; D014902:West Nile virus / Q000235:genetics / Q000254:growth & development / Q000276:immunology
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; D053060:West Nile Virus Vaccines; C531936:nonstructural protein 1, West Nile virus