4.5 Article

Development and characterization of non-glycosylated E and NS1 mutant viruses as a potential candidate vaccine for West Nile virus

期刊

VACCINE
卷 28, 期 4, 页码 1075-1083

出版社

ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2009.10.112

关键词

West Nile virus; Attenuation; Glycosylation

资金

  1. Clayton Foundation for Research
  2. Medical Research Council [G116/194] Funding Source: researchfish
  3. MRC [G116/194] Funding Source: UKRI

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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 1000 PFU 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 50 PFU (C) 2009 Elsevier Ltd All rights reserved.

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