BACKGROUND: West Nile virus (WNV) is a flavivirus that causes meningitis and encephalitis. There are no licensed vaccines to prevent WNV in humans. The safety and immunogenicity of a first-generation WNV DNA vaccine was demonstrated in a clinical trial and a similar DNA vaccine has been licensed for use in horses. METHODS: A DNA vaccine encoding the protein premembrane and the E glycoproteins of the NY99 strain of WNV under the transcriptional control of the CMV/R promoter was evaluated in an open-label study in 30 healthy adults. Half of the subjects were age 18-50 years and half were age 51-65 years. Immune responses were assessed by enzyme-linked immunosorbent assay, neutralization assays, intracellular cytokine staining, and ELISpot. RESULTS: The 3-dose vaccine regimen was safe and well tolerated. Vaccine-induced T cell and neutralizing antibody responses were detected in the majority of subjects. The antibody responses seen in the older age group were of similar frequency, magnitude, and duration as those seen in the younger cohort. CONCLUSIONS: Neutralizing antibody responses to WNV were elicited by DNA vaccination in humans, including in older individuals, where responses to traditional vaccine approaches are often diminished. This DNA vaccine elicited T cell responses of greater magnitude when compared with an earlier-generation construct utilizing a CMV promoter. CLINICAL TRIALS REGISTRATION: NCT00300417.
BACKGROUND:West Nile virus (WNV) is a flavivirus that causes meningitis and encephalitis. There are no licensed vaccines to prevent WNV in humans. The safety and immunogenicity of a first-generation WNV DNA vaccine was demonstrated in a clinical trial and a similar DNA vaccine has been licensed for use in horses. METHODS: A DNA vaccine encoding the protein premembrane and the E glycoproteins of the NY99 strain of WNV under the transcriptional control of the CMV/R promoter was evaluated in an open-label study in 30 healthy adults. Half of the subjects were age 18-50 years and half were age 51-65 years. Immune responses were assessed by enzyme-linked immunosorbent assay, neutralization assays, intracellular cytokine staining, and ELISpot. RESULTS: The 3-dose vaccine regimen was safe and well tolerated. Vaccine-induced T cell and neutralizing antibody responses were detected in the majority of subjects. The antibody responses seen in the older age group were of similar frequency, magnitude, and duration as those seen in the younger cohort. CONCLUSIONS: Neutralizing antibody responses to WNV were elicited by DNA vaccination in humans, including in older individuals, where responses to traditional vaccine approaches are often diminished. This DNA vaccine elicited T cell responses of greater magnitude when compared with an earlier-generation construct utilizing a CMV promoter. CLINICAL TRIALS REGISTRATION: NCT00300417.
Authors: David Holland; Robert Booy; Ferdinandus De Looze; Peter Eizenberg; James McDonald; Jeff Karrasch; Maureen McKeirnan; Hatem Salem; Graham Mills; Jim Reid; Françoise Weber; Melanie Saville Journal: J Infect Dis Date: 2008-09-01 Impact factor: 5.226
Authors: John H Beigel; Jeffrey L Nordstrom; Stanley R Pillemer; Cory Roncal; D Ronald Goldwater; Hua Li; P Chris Holland; Syd Johnson; Kathryn Stein; Scott Koenig Journal: Antimicrob Agents Chemother Date: 2010-03-29 Impact factor: 5.191
Authors: Hannah Kibuuka; Robert Kimutai; Leonard Maboko; Fred Sawe; Mirjam S Schunk; Arne Kroidl; Douglas Shaffer; Leigh Anne Eller; Rukia Kibaya; Michael A Eller; Karin B Schindler; Alexandra Schuetz; Monica Millard; Jason Kroll; Len Dally; Michael Hoelscher; Robert Bailer; Josephine H Cox; Mary Marovich; Deborah L Birx; Barney S Graham; Nelson L Michael; Mark S de Souza; Merlin L Robb Journal: J Infect Dis Date: 2010-02-15 Impact factor: 5.226
Authors: Gunther Spohn; Gary T Jennings; Byron Ee Martina; Iris Keller; Markus Beck; Paul Pumpens; Albert Dme Osterhaus; Martin F Bachmann Journal: Virol J Date: 2010-07-06 Impact factor: 4.099
Authors: Julie E Martin; Mark K Louder; LaSonji A Holman; Ingelise J Gordon; Mary E Enama; Brenda D Larkin; Charla A Andrews; Leatrice Vogel; Richard A Koup; Mario Roederer; Robert T Bailer; Phillip L Gomez; Martha Nason; John R Mascola; Gary J Nabel; Barney S Graham Journal: Vaccine Date: 2008-09-26 Impact factor: 3.641
Authors: Bruce S Thompson; Bastiaan Moesker; Jolanda M Smit; Jan Wilschut; Michael S Diamond; Daved H Fremont Journal: PLoS Pathog Date: 2009-05-29 Impact factor: 6.823
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: Ram Narayan Trivedi; Parvez Akhtar; Jonathan Meade; Patrick Bartlow; Mohammad M Ataai; Saleem A Khan; Michael M Domach Journal: Appl Environ Microbiol Date: 2014-09-12 Impact factor: 4.792
Authors: Kimberly A Dowd; Sung-Youl Ko; Kaitlyn M Morabito; Eun Sung Yang; Rebecca S Pelc; Christina R DeMaso; Leda R Castilho; Peter Abbink; Michael Boyd; Ramya Nityanandam; David N Gordon; John Robert Gallagher; Xuejun Chen; John-Paul Todd; Yaroslav Tsybovsky; Audray Harris; Yan-Jang S Huang; Stephen Higgs; Dana L Vanlandingham; Hanne Andersen; Mark G Lewis; Rafael De La Barrera; Kenneth H Eckels; Richard G Jarman; Martha C Nason; Dan H Barouch; Mario Roederer; Wing-Pui Kong; John R Mascola; Theodore C Pierson; Barney S Graham Journal: Science Date: 2016-09-22 Impact factor: 47.728
Authors: Nikolai Petrovsky; Maximilian Larena; Venkatraman Siddharthan; Natalie A Prow; Roy A Hall; Mario Lobigs; John Morrey Journal: J Virol Date: 2013-07-17 Impact factor: 5.103