While the outbreak of ZIKV in the Americas is likely to subside in the next 1-2 years, there is going to be an ongoing risk of congenital Zika syndrome in babies born to mothers exposed to ZIKV during pregnancy. There is no licensed vaccine or treatment to combat ZIKV infection. Because of the urgent need for a ZIKV vaccine, and a finite time in which efficacy could be demonstrated in the current outbreak, we focused on developing a DNA vaccine, which can be rapidly produced and can easily modified using reverse genetics techniques. The first generation DNA vaccines are based on prior success in West Nile Virus. We designed and evaluated two lead DNA vaccine candidates which produce subviral particles (SVP) after transfection. The first candidate (VRC5283) expresses the prM and E proteins from the ZIKV French Polynesia 2014 strain. The other (VRC5288) is a ZIKV/JEV chimera virus and was designed with the final 98 amino acids of (comprising the transmembrane and stem domains from JEV) swapped for the corresponding regions from ZIKV which has been demonstrated to improve SVP secretion for other flaviviruses. Immunization with these constructs generated robust neutralizing antibody responses in mice and rhesus macaques. Two doses of DNA vaccine candidates expressing the prM and E proteins of Zika virus protected 17 out of 18 rhesus macaques from viremia after Zika virus challenge. This protection was correlated with serum neutralizing activity. A single dose of DNA vaccine did not completely prevent infection, but significantly reduced the level of viremia in Zika virus challenged rhesus macaques.

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Gaudinski, Martin R; Houser, Katherine V; Morabito, Kaitlyn M et al. (2018) Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: randomised, open-label, phase 1 clinical trials. Lancet 391:552-562
Goo, Leslie; DeMaso, Christina R; Pelc, Rebecca S et al. (2018) The Zika virus envelope protein glycan loop regulates virion antigenicity. Virology 515:191-202
Morabito, Kaitlyn M; Graham, Barney S (2017) Zika Virus Vaccine Development. J Infect Dis 216:S957-S963
Shan, Chao; Muruato, Antonio E; Jagger, Brett W et al. (2017) A single-dose live-attenuated vaccine prevents Zika virus pregnancy transmission and testis damage. Nat Commun 8:676
Pierson, Theodore C; Graham, Barney S (2016) Zika Virus: Immunity and Vaccine Development. Cell 167:625-631
Dowd, Kimberly A; DeMaso, Christina R; Pelc, Rebecca S et al. (2016) Broadly Neutralizing Activity of Zika Virus-Immune Sera Identifies a Single Viral Serotype. Cell Rep 16:1485-1491
Dowd, Kimberly A; Ko, Sung-Youl; Morabito, Kaitlyn M et al. (2016) Rapid development of a DNA vaccine for Zika virus. Science 354:237-240
Tumurkhuu, Gantsetseg; Dagvadorj, Jargalsaikhan; Jones, Heather D et al. (2015) Alternatively spliced myeloid differentiation protein-2 inhibits TLR4-mediated lung inflammation. J Immunol 194:1686-94