A West Nile Virus DNA Vaccine Induces Neutralizing Antibody in Healthy Adults during a Phase 1 Clinical Trial

Abstract

Background. West Nile virus (WNV) is a mosquitoborne 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.

Secretion of dengue virus envelope protein ectodomain from mammalian cells is dependent on domain II serotype and affects the immune response upon DNA vaccination

“…Since the first human clinical trial for a DNA vaccine against human immunodeficiency virus (MacGregor et al, 1998), several other candidates have been developed and tested in Phase 1 studies against a wide variety of infectious diseases (Graham et al, 2006;Ledgerwood et al, 2011;Martin et al, 2006Martin et al, , 2007Sarwar et al, 2015). Although there are a number of studies describing DNA vaccines against dengue Azevedo et al, 2011;Galula et al, 2014;Khanam et al, 2006;Konishi et al, 2006;Ocazionez Jimenez & Lopes da Fonseca, 2000;Prompetchara et al, 2014;Ramanathan et al, 2009;Raviprakash et al, 2001Raviprakash et al, , 2006, to date there has been only one human clinical trial for a dengue DNA vaccine involving a Phase 1 study of a plasmid expressing the PrM and E proteins of DENV1 .…”

Plasmids encoding the mucosal chemokines CCL27 and CCL28 are effective adjuvants in eliciting antigen-specific immunity in vivo

“…[12][13][14][15][16][17] These strategies have shown promise in improving the efficacy of DNA vaccines in large-animal models such as horses, dogs and pigs, as well as in humans. 2,[18][19][20][21][22] Currently, several DNAbased veterinary products have been licensed for use. 2 One strategy that improves the immunogenicity of DNA vaccines is the use of chemokine molecular adjuvants.…”

Recent advances in human flavivirus vaccines

“…[41]. Furthermore, all subjects developed neutralising antibodies at levels comparable to those seen in horses known to be protective.…”