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.
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, United States.
authors.forename: Travis J
authors.initials: TJ
authors.lastname: Taylor
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, United States.
authors.forename: Fernando
authors.initials: F
authors.lastname: Diaz
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, United States.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Colgrove
authors.affiliation: Wadsworth Center, New York State Department of Health, P.O Box 509, Albany, NY 12201, United States.
authors.forename: Kristen A
authors.initials: KA
authors.lastname: Bernard
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, 523 Bridgeside Point II, 450 Technology Drive, Pittsburgh, PA 15261, United States.
authors.forename: Neal A
authors.initials: NA
authors.lastname: DeLuca
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, United States.
authors.forename: Sean P J
authors.initials: SPJ
authors.lastname: Whelan
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, United States. Electronic address: david_knipe@hms.harvard.edu.
authors.forename: David M
authors.initials: DM
authors.lastname: Knipe
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D002213:Capsid / Q000276:immunology / Q000648:ultrastructure; D002460:Cell Line; D023061:Gene Order; D005822:Genetic Vectors / Q000235:genetics*; D018259:Herpesvirus 1, Human / Q000235:genetics*; D006801:Humans; D007114:Immunization; D051379:Mice; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology / Q000648:ultrastructure; D015678:Viral Structural Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D014902:West Nile virus / Q000235:genetics* / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D058425:Vaccines, Virus-Like Particle; D015678:Viral Structural Proteins
keywords: Flavivirus; HSV recombinant vector; Vaccine vector; West Nile virus; Zika virus