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

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• 作者：Drew Hannaman^a ; ¹ ; Lesley C. Dupuy^b ; ¹ ; Barry Ellefsen^a ; Connie S. Schmaljohn^b ; ^{connie.s.schmaljohn.civ@mail.mil" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Venezuelan equine encephalitis ; DNA vaccine ; Electroporation ; Intramuscular ; Intradermal ; Human ; Clinical trial ; Phase 1
• 刊名：Vaccine
• 出版年：2016
• 出版时间：30 June 2016
• 年：2016
• 卷：34
• 期：31
• 页码：3607-3612
• 全文大小：784 K

文摘

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 0.5 mg (N = 8) or 2.0 mg (N = 9) of pWRG/VEE or a saline placebo (N = 4) in a 1.0 ml injection. Subjects in ID-EP groups received 0.08 mg (N = 8) or 0.3 mg (N = 8) of DNA or a saline placebo (N = 4) in a 0.15 ml 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.