Production of immunogenic West Nile virus-like particles using a herpes simplex virus 1 recombinant vector

Travis J. Taylor; Fernando Diaz; Robert C. Colgrove; Kristen A. Bernard; Neal A. DeLuca; Sean P.J. Whelan; David M. Knipe

doi:10.1016/j.virol.2016.06.006

Production of immunogenic West Nile virus-like particles using a herpes simplex virus 1 recombinant vector

Travis J. Taylor, Fernando Diaz, Robert C. Colgrove, Kristen A. Bernard, Neal A. DeLuca, Sean P.J. Whelan, David M. Knipe

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

Abstract

West Nile virus (WNV) is a flavivirus that swept rapidly across North America in 1999, declined in prevalence, and then resurged in 2012. To date, no vaccine is available to prevent infection in the human population. Herpes simplex virus (HSV) replication-defective vaccine vectors induce a durable immunity characterized by strong antibody and CD8⁺ T cell responses even in HSV-immune animals. In this study, a WNV protein expression cassette was optimized for virus-like particle (VLP) production in transfection studies, and the cassette was recombined into an HSV-1 d106-WNV virus vector, which produced extracellular VLPs, as confirmed by immunoelectron microscopy. Immunization of mice with the d106-WNV recombinant vector elicited a specific anti-WNV IgG response. This study highlights the flavivirus coding sequences needed for efficient assembly of virus-like particles. This information will facilitate generation of additional vaccine vectors against other flaviviruses including the recently emerged Zika virus.

Original language	English
Pages (from-to)	186-193
Number of pages	8
Journal	Virology
Volume	496
DOIs	https://doi.org/10.1016/j.virol.2016.06.006
State	Published - Sep 1 2016

Keywords

Flavivirus
HSV recombinant vector
Vaccine vector
West Nile virus
Zika virus

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10.1016/j.virol.2016.06.006

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title = "Production of immunogenic West Nile virus-like particles using a herpes simplex virus 1 recombinant vector",

abstract = "West Nile virus (WNV) is a flavivirus that swept rapidly across North America in 1999, declined in prevalence, and then resurged in 2012. To date, no vaccine is available to prevent infection in the human population. Herpes simplex virus (HSV) replication-defective vaccine vectors induce a durable immunity characterized by strong antibody and CD8+ T cell responses even in HSV-immune animals. In this study, a WNV protein expression cassette was optimized for virus-like particle (VLP) production in transfection studies, and the cassette was recombined into an HSV-1 d106-WNV virus vector, which produced extracellular VLPs, as confirmed by immunoelectron microscopy. Immunization of mice with the d106-WNV recombinant vector elicited a specific anti-WNV IgG response. This study highlights the flavivirus coding sequences needed for efficient assembly of virus-like particles. This information will facilitate generation of additional vaccine vectors against other flaviviruses including the recently emerged Zika virus.",

keywords = "Flavivirus, HSV recombinant vector, Vaccine vector, West Nile virus, Zika virus",

author = "Taylor, {Travis J.} and Fernando Diaz and Colgrove, {Robert C.} and Bernard, {Kristen A.} and DeLuca, {Neal A.} and Whelan, {Sean P.J.} and Knipe, {David M.}",

note = "Funding Information: We thank Kim Appler for her technical assistance with the antibody analysis, Maria Ericsson for her assistance with electron microscopy, Gus Kousoulis for plasmids, and Patrick T. Waters for assistance with preparation of the manuscript. This research was supported by NIAID grants U54-AI057159 (New England Regional Center for Excellence in Biodefense and Emerging Infections) and U54-AI057158 (Northeast Biodefense Center) and R01 AI057552 to DMK and U19-AI109740 to SPJW. Publisher Copyright: {\textcopyright} 2016.",

year = "2016",

month = sep,

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doi = "10.1016/j.virol.2016.06.006",

language = "English",

volume = "496",

pages = "186--193",

journal = "Virology",

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AU - Taylor, Travis J.

AU - Diaz, Fernando

AU - Colgrove, Robert C.

AU - Bernard, Kristen A.

AU - DeLuca, Neal A.

AU - Whelan, Sean P.J.

AU - Knipe, David M.

N1 - Funding Information: We thank Kim Appler for her technical assistance with the antibody analysis, Maria Ericsson for her assistance with electron microscopy, Gus Kousoulis for plasmids, and Patrick T. Waters for assistance with preparation of the manuscript. This research was supported by NIAID grants U54-AI057159 (New England Regional Center for Excellence in Biodefense and Emerging Infections) and U54-AI057158 (Northeast Biodefense Center) and R01 AI057552 to DMK and U19-AI109740 to SPJW. Publisher Copyright: © 2016.

PY - 2016/9/1

Y1 - 2016/9/1

N2 - West Nile virus (WNV) is a flavivirus that swept rapidly across North America in 1999, declined in prevalence, and then resurged in 2012. To date, no vaccine is available to prevent infection in the human population. Herpes simplex virus (HSV) replication-defective vaccine vectors induce a durable immunity characterized by strong antibody and CD8+ T cell responses even in HSV-immune animals. In this study, a WNV protein expression cassette was optimized for virus-like particle (VLP) production in transfection studies, and the cassette was recombined into an HSV-1 d106-WNV virus vector, which produced extracellular VLPs, as confirmed by immunoelectron microscopy. Immunization of mice with the d106-WNV recombinant vector elicited a specific anti-WNV IgG response. This study highlights the flavivirus coding sequences needed for efficient assembly of virus-like particles. This information will facilitate generation of additional vaccine vectors against other flaviviruses including the recently emerged Zika virus.

AB - West Nile virus (WNV) is a flavivirus that swept rapidly across North America in 1999, declined in prevalence, and then resurged in 2012. To date, no vaccine is available to prevent infection in the human population. Herpes simplex virus (HSV) replication-defective vaccine vectors induce a durable immunity characterized by strong antibody and CD8+ T cell responses even in HSV-immune animals. In this study, a WNV protein expression cassette was optimized for virus-like particle (VLP) production in transfection studies, and the cassette was recombined into an HSV-1 d106-WNV virus vector, which produced extracellular VLPs, as confirmed by immunoelectron microscopy. Immunization of mice with the d106-WNV recombinant vector elicited a specific anti-WNV IgG response. This study highlights the flavivirus coding sequences needed for efficient assembly of virus-like particles. This information will facilitate generation of additional vaccine vectors against other flaviviruses including the recently emerged Zika virus.

KW - Flavivirus

KW - HSV recombinant vector

KW - Vaccine vector

KW - West Nile virus

KW - Zika virus

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Production of immunogenic West Nile virus-like particles using a herpes simplex virus 1 recombinant vector

Abstract

Keywords

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