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

Melissa C. Whiteman; Li Li; Jason A. Wicker; Richard M. Kinney; Claire Huang; David W.C. Beasley; Kyung Min Chung; Michael S. Diamond; Tom Solomon; Alan D.T. Barrett

doi:10.1016/j.vaccine.2009.10.112

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

Melissa C. Whiteman, Li Li, Jason A. Wicker, Richard M. Kinney, Claire Huang, David W.C. Beasley, Kyung Min Chung, Michael S. Diamond, Tom Solomon, Alan D.T. Barrett

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64 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1075-1083
Number of pages	9
Journal	Vaccine
Volume	28
Issue number	4
DOIs	https://doi.org/10.1016/j.vaccine.2009.10.112
State	Published - Jan 22 2010

Keywords

Attenuation
Glycosylation
West Nile virus

ASJC Scopus subject areas

Molecular Medicine
General Immunology and Microbiology
General Veterinary
Public Health, Environmental and Occupational Health
Infectious Diseases

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10.1016/j.vaccine.2009.10.112

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

abstract = "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 E154S/NS1130A/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 E154S/NS1130A/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.",

keywords = "Attenuation, Glycosylation, West Nile virus",

author = "Whiteman, {Melissa C.} and Li Li and Wicker, {Jason A.} and Kinney, {Richard M.} and Claire Huang and Beasley, {David W.C.} and Chung, {Kyung Min} and Diamond, {Michael S.} and Tom Solomon and Barrett, {Alan D.T.}",

note = "Funding Information: We would like to thank Nivia S. Radzieski for technical assistance and the UTMB Protein Chemistry Core for sequencing. This work was supported in part by the Clayton Foundation for Research .",

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AU - Whiteman, Melissa C.

AU - Li, Li

AU - Wicker, Jason A.

AU - Kinney, Richard M.

AU - Huang, Claire

AU - Beasley, David W.C.

AU - Chung, Kyung Min

AU - Diamond, Michael S.

AU - Solomon, Tom

AU - Barrett, Alan D.T.

N1 - Funding Information: We would like to thank Nivia S. Radzieski for technical assistance and the UTMB Protein Chemistry Core for sequencing. This work was supported in part by the Clayton Foundation for Research .

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N2 - 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 E154S/NS1130A/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 E154S/NS1130A/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.

AB - 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 E154S/NS1130A/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 E154S/NS1130A/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.

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

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Keywords

ASJC Scopus subject areas

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