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A West Nile Virus DNA Vaccine Utilizing a Modified Promoter Induces Neutralizing Antibody in Younger and Older Healthy Adults in a Phase I Clinical Trial

  作者 Ledgerwood, JE; Pierson, TC; Hubka, SA; Desai, N; Rucker, S; Gordon, IJ; Enama, ME; Nelson, S; Nason, M; Gu, WJ; Bundrant, N; Koup, RA; Bailer, RT; Mascola, JR; Nabel, GJ; Graham, BS  
  选自 期刊  Journal of Infectious Diseases;  卷期  2011年203-10;  页码  1396-1404  
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[摘要]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.

 
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