title: A heterologous DNA prime-Venezuelan equine encephalitis virus replicon particle boost dengue vaccine regimen affords complete protection from virus challenge in cynomolgus macaques.
abstract: A candidate vaccine (D1ME-VRP) expressing dengue virus type 1 premembrane and envelope proteins in a Venezuelan equine encephalitis (VEE) virus replicon particle (VRP) system was constructed and tested in conjunction with a plasmid DNA vaccine (D1ME-DNA) expressing identical dengue virus sequences. Cynomolgus macaques were vaccinated with three doses of DNA (DDD), three doses of VRP (VVV group), or a heterologous DNA prime-VRP boost regimen (DDV) using two doses of DNA vaccine and a third dose of VRP vaccine. Four weeks after the final immunization, the DDV group produced the highest dengue virus type 1-specific immunoglobulin G antibody responses and virus-neutralizing antibody titers. Moderate T-cell responses were demonstrated only in DDD- and DDV-vaccinated animals. When vaccinated animals were challenged with live virus, all vaccination regimens showed significant protection from viremia. DDV-immunized animals were completely protected from viremia (mean time of viremia = 0 days), whereas DDD- and VVV-vaccinated animals had mean times of viremia of 0.66 and 0.75 day, respectively, compared to 6.33 days for the control group of animals.
authors: Viral and Rickettsial Diseases Department, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA.
authors: Lan
authors: L
authors: Chen
authors: Dan
authors: D
authors: Ewing
authors: Hemavathy
authors: H
authors: Subramanian
authors: Karla
authors: K
authors: Block
authors: Jonathan
authors: J
authors: Rayner
authors: Kimberly D
authors: KD
authors: Alterson
authors: Martha
authors: M
authors: Sedegah
authors: Curtis
authors: C
authors: Hayes
authors: Kevin
authors: K
authors: Porter
authors: Kanakatte
authors: K
authors: Raviprakash
mesh_terms: D000818:Animals; D004267:DNA Viruses / Q000737:chemistry*; D004666:Encephalitis Virus, Venezuelan Equine / Q000235:genetics*; D004685:Encephalomyelitis, Venezuelan Equine / Q000276:immunology / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007107:Immune System; D007114:Immunization; D007074:Immunoglobulin G / Q000737:chemistry; D007371:Interferon-gamma / Q000378:metabolism; D008251:Macaca; D008297:Male; D012093:Replicon; D013601:T-Lymphocytes / Q000821:virology; D014765:Viral Vaccines / Q000737:chemistry*
chemical_list: D007074:Immunoglobulin G; D014765:Viral Vaccines; D007371:Interferon-gamma
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