A Phase 1 clinical trial of a DNA vaccine for Venezuelan equine encephalitis delivered by intramuscular or intradermal electroporation

• Published in: Vaccine Vol. 34; no. 31; pp. 3607 - 3612
• Main Authors: Hannaman, Drew, Dupuy, Lesley C., Ellefsen, Barry, Schmaljohn, Connie S.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 30.06.2016; Elsevier Limited
• Subjects: Adolescent; Adult; Allergy and Immunology; Alphavirus; antibodies; Antibodies, Neutralizing - blood; Antibodies, Viral - blood; Clinical trial; clinical trials; Deoxyribonucleic acid; DNA; DNA vaccine; Double-Blind Method; Electroporation; Encephalitis; Encephalitis Virus, Venezuelan Equine; Encephalomyelitis, Venezuelan Equine - prevention & control; Female; genes; Hispanic Americans; horses; Human; Humans; immune response; Immunogenicity; Immunogenicity, Vaccine; Immunoglobulins; Injection; Injections, Intradermal; Injections, Intramuscular; Intradermal; Intramuscular; Male; Middle Aged; Phase 1; questionnaires; R&D; recombinant vaccines; Reoviridae; Research & development; Studies; Togaviridae; Vaccines; Vaccines, DNA - administration & dosage; Vaccines, DNA - therapeutic use; Venezuelan equine encephalitis; Venezuelan equine encephalitis virus; Viral Vaccines - administration & dosage; Viral Vaccines - therapeutic use; Young Adult; DNA vaccine; Human; Intradermal; Venezuelan equine encephalitis; Electroporation; Clinical trial; Intramuscular; Phase 1
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2016.04.077

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.