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N Engl J Med. 2017 Oct 4. doi: 10.1056/NEJMoa1708120. [Epub ahead of print]

Safety and Immunogenicity of an Anti-Zika Virus DNA Vaccine - Preliminary Report.

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From the Division of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania (P.T.), and Wistar Institute (K.M., E.L.R., S.B.K., F.I.Z., H.C., D.B.W.), Philadelphia, and Inovio Pharmaceuticals, Plymouth Meeting (S.W., A.S.K., J.B., M.B.) - all in Pennsylvania; GeneOne Life Science, Seoul, South Korea (C.C.R., Y.K.P., C.R., S.E.S., J.N.M.); Infectious Diseases Research Centre-Université Laval, Quebec, QC, Canada (T.R., S.T., G.P.K.); QPS-Miami Research Associates, Miami, (D.K.); and the Department of Medicine, Morristown Medical Center, Morristown, NJ (J.N.M.).


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 number, NCT02809443 .).

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