title: A Phase 1 clinical trial of a DNA vaccine for Venezuelan equine encephalitis delivered by intramuscular or intradermal electroporation.
abstract: Venezuelan equine encephalitis virus (VEEV), a mosquito-borne alphavirus, causes periodic epizootics in equines and is a recognized biological defense threat for humans. There are currently no FDA-licensed vaccines against VEEV. We developed a candidate DNA vaccine expressing the E3-E2-6K-E1 genes of VEEV (pWRG/VEE) and performed a Phase 1 clinical study to assess the vaccine's safety, reactogenicity, tolerability, and immunogenicity when administered by intramuscular (IM) or intradermal (ID) electroporation (EP) using the Ichor Medical Systems TriGrid™ Delivery System. Subjects in IM-EP groups received 0.5mg (N=8) or 2.0mg (N=9) of pWRG/VEE or a saline placebo (N=4) in a 1.0ml injection. Subjects in ID-EP groups received 0.08mg (N=8) or 0.3mg (N=8) of DNA or a saline placebo (N=4) in a 0.15ml injection. Subjects were monitored for a total period of 360 days. No vaccine- or device-related serious adverse events were reported. Based on the results of a subject questionnaire, the IM- and ID-EP procedures were both considered to be generally acceptable for prophylactic vaccine administration, with the acute tolerability of ID EP delivery judged to be greater than that of IM-EP delivery. All subjects (100%) in the high and low dose IM-EP groups developed detectable VEEV-neutralizing antibodies after two or three administrations of pWRG/VEE, respectively. VEEV-neutralizing antibody responses were detected in seven of eight subjects (87.5%) in the high dose and five of eight subjects (62.5%) in the low dose ID-EP groups after three vaccine administrations. There was a correlation between the DNA dose and the magnitude of the resulting VEEV-neutralizing antibody responses for both IM and ID EP delivery. These results indicate that pWRG/VEE delivered by either IM- or ID-EP is safe, tolerable, and immunogenic in humans at the evaluated dose levels. Clinicaltrials.gov registry number NCT01984983.
authors.affiliation: Ichor Medical Systems, Inc., San Diego, CA, USA.
authors.forename: Drew
authors.initials: D
authors.lastname: Hannaman
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA.
authors.forename: Lesley C
authors.initials: LC
authors.lastname: Dupuy
authors.affiliation: Ichor Medical Systems, Inc., San Diego, CA, USA.
authors.forename: Barry
authors.initials: B
authors.lastname: Ellefsen
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA. Electronic address: connie.s.schmaljohn.civ@mail.mil.
authors.forename: Connie S
authors.initials: CS
authors.lastname: Schmaljohn
mesh_terms: D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D004311:Double-Blind Method; D018274:Electroporation; D004666:Encephalitis Virus, Venezuelan Equine; D004685:Encephalomyelitis, Venezuelan Equine / Q000517:prevention & control*; D005260:Female; D006801:Humans; D000071497:Immunogenicity, Vaccine; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000627:therapeutic use; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019444:Vaccines, DNA; D014765:Viral Vaccines
keywords: Clinical trial; DNA vaccine; Electroporation; Human; Intradermal; Intramuscular; Phase 1; Venezuelan equine encephalitis