A West Nile virus DNA vaccine induces neutralizing antibody in healthy adults during a phase 1 clinical trial.
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.


BACKGROUND
ClinicalTrials.gov identifier: NCT00106769 .
Martin
Julie E
JE
Vaccine Research Center, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD 20892, USA.
Pierson
Theodore C
TC
Hubka
Sarah
S
Rucker
Steve
S
Gordon
Ingelise J
IJ
Enama
Mary E
ME
Andrews
Charla A
CA
Xu
Qing
Q
Davis
Brent S
BS
Nason
Martha
M
Fay
Michael
M
Koup
Richard A
RA
Roederer
Mario
M
Bailer
Robert T
RT
Gomez
Phillip L
PL
Mascola
John R
JR
Chang
Gwong-Jen J
GJ
Nabel
Gary J
GJ
Graham
Barney S
BS
D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use* / Q000821:virology; D014901:West Nile Fever / Q000517:prevention & control* / Q000821:virology; D053060:West Nile Virus Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D014902:West Nile virus / Q000235:genetics / Q000276:immunology*
D000914:Antibodies, Viral; D019444:Vaccines, DNA; D053060:West Nile Virus Vaccines