Pablo Tebas,et al.

Background:Although Zika virus (ZIKV) infection is typically self-limiting,other associated complications such as congenital birth defects and the Guillain-Barré syndrome are well described.There are no approved vaccines against ZIKV infection.

Methods:In this phase 1,open-label clinical trial,we evaluated the safety and immunogenicity of a synthetic,consensus DNA vaccine (GLS-5700) encoding the ZIKV premembrane and envelope proteins in two groups of 20 participants each.The participants received either 1 mg or 2 mg of vaccine intradermally,with each injection followed by electroporation (the use of a pulsed electric field to introduce the DNA sequence into cells) at baseline,4 weeks,and 12 weeks.

Results:The median age of the participants was 38 years,and 60% were women;78% were White and 22% Black;in addition,30% were Hispanic.At the interim analysis at 14 weeks (i.e.,after the third dose of vaccine),no serious adverse events were reported.Local reactions at the vaccination site (e.g.,injection-site pain,redness,swelling,and itching) occurred in approximately 50% of the participants.After the third dose of vaccine,binding antibodies (as measured on enzyme-linked immunosorbent assay)were detected in all the participants,with geometric mean titers of 1642 and 2871 in recipients of 1 mg and 2 mg of vaccine,respectively.Neutralizing antibodies developed in 62% of the samples on Vero-cell assay.On neuronal-cell assay,there was 90%inhibition of ZIKV infection in 70% of the serum samples and 50% inhibition in 95% of the samples.The intraperitoneal injection of postvaccination serum protected 103 of 112 IFNAR knockout mice (bred with deletion of genes encoding interferon-α and interferon-β receptors) (92%) that were challenged with a lethal dose of ZIKV-PR209 strain;none of the mice receiving baseline serum survived the challenge.Survival was independent of the neutralization titer.

Conclusions:In this phase 1,open-label clinical trial,a DNA vaccine elicited anti-ZIKV immune responses.Further studies are needed to better evaluate the safety and efficacy of the vaccine.(Funded by GeneOne Life Science and others;ZIKA-001 ClinicalTrials.gov number,NCT02809443.).