BACKGROUND: West Nile virus (WNV) is a mosquito-borne flavivirus that can cause severe meningitis and encephalitis in infected individuals. We report the safety and immunogenicity of a WNV DNA vaccine in its first phase 1 human study. METHODS: A single-plasmid DNA vaccine encoding the premembrane and the envelope glycoproteins of the NY99 strain of WNV was evaluated in an open-label study in 15 healthy adults. Twelve subjects completed the 3-dose vaccination schedule, and all subjects completed 32 weeks of evaluation for safety and immunogenicity. The development of a vaccine-induced immune response was assessed by enzyme-linked immunosorbant assay, neutralization assays, intracelluar cytokine staining, and enzyme-linked immunospot assay. RESULTS: The vaccine was safe and well tolerated, with no significant adverse events. Vaccine-induced T cell and antibody responses were detected in the majority of subjects. Neutralizing antibody to WNV was detected in all subjects who completed the 3-dose vaccination schedule, at levels shown to be protective in studies of horses, an incidental natural host for WNV. CONCLUSIONS: Further assessment of this DNA platform for human immunization against WNV is warranted. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00106769 .
BACKGROUND:West Nile virus (WNV) is a mosquito-borne flavivirus that can cause severe meningitis and encephalitis in infected individuals. We report the safety and immunogenicity of a WNV DNA vaccine in its first phase 1 human study. METHODS: A single-plasmid DNA vaccine encoding the premembrane and the envelope glycoproteins of the NY99 strain of WNV was evaluated in an open-label study in 15 healthy adults. Twelve subjects completed the 3-dose vaccination schedule, and all subjects completed 32 weeks of evaluation for safety and immunogenicity. The development of a vaccine-induced immune response was assessed by enzyme-linked immunosorbant assay, neutralization assays, intracelluar cytokine staining, and enzyme-linked immunospot assay. RESULTS: The vaccine was safe and well tolerated, with no significant adverse events. Vaccine-induced T cell and antibody responses were detected in the majority of subjects. Neutralizing antibody to WNV was detected in all subjects who completed the 3-dose vaccination schedule, at levels shown to be protective in studies of horses, an incidental natural host for WNV. CONCLUSIONS: Further assessment of this DNA platform for human immunization against WNV is warranted. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00106769 .
Authors: Elliott R Jacobson; Pamela E Ginn; J Mitchell Troutman; Lisa Farina; Lillian Stark; Kaci Klenk; Kristen L Burkhalter; Nicholas Komar Journal: J Wildl Dis Date: 2005-01 Impact factor: 1.535
Authors: Bruno P Granwehr; Kristy M Lillibridge; Stephen Higgs; Peter W Mason; Judith F Aronson; Gerald A Campbell; Alan D T Barrett Journal: Lancet Infect Dis Date: 2004-09 Impact factor: 25.071
Authors: Patricia Salazar; Josie L Traub-Dargatz; Paul S Morley; Delwin D Wilmot; David J Steffen; Wayne E Cunningham; M D Salman Journal: J Am Vet Med Assoc Date: 2004-07-15 Impact factor: 1.936
Authors: J M Minke; L Siger; K Karaca; L Austgen; P Gordy; R Bowen; R W Renshaw; S Loosmore; J C Audonnet; B Nordgren Journal: Arch Virol Suppl Date: 2004
Authors: John T Watson; Peter E Pertel; Roderick C Jones; Alicia M Siston; William S Paul; Constance C Austin; Susan I Gerber Journal: Ann Intern Med Date: 2004-09-07 Impact factor: 25.391
Authors: Julie E Ledgerwood; Zonghui Hu; Pamela Costner; Galina Yamshchikov; Mary E Enama; Sarah Plummer; Cynthia S Hendel; Lasonji Holman; Brenda Larkin; Ingelise Gordon; Robert T Bailer; Donald M Poretz; Uzma Sarwar; Alisha Kabadi; Richard Koup; John R Mascola; Barney S Graham Journal: Contemp Clin Trials Date: 2015-08-12 Impact factor: 2.226
Authors: Marina T Siirin; Amelia P A Travassos da Rosa; Patrick Newman; Carolyn Weeks-Levy; Beth-Ann Coller; Shu-Yuan Xiao; Michael M Lieberman; Douglas M Watts Journal: Am J Trop Med Hyg Date: 2008-12 Impact factor: 2.345
Authors: Nathalie Bonafé; Joseph A Rininger; Richard G Chubet; Harald G Foellmer; Stacey Fader; John F Anderson; Sandra L Bushmich; Karen Anthony; Michel Ledizet; Erol Fikrig; Raymond A Koski; Paul Kaplan Journal: Vaccine Date: 2008-11-07 Impact factor: 3.641