Journal
JOURNAL OF VIROLOGY
Volume 81, Issue 21, Pages 11634-11639Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.00996-07
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A candidate vaccine (D1ME-VR-P) expressing dengue virus type I premembrane and envelope proteins in a Venezuelan equine encephalitis (VEE) virus replicon particle (VR-P) system was constructed and tested in conjunction with a plasmid DNA vaccine (DIME-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 I-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.
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