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. Subsequently, we have continued to study the two DNA vaccines by performing dose de-escalation studies to determine the neutralizing antibody threshold of protection, and correlates of protection. Additionally, we have collaborated with multiple groups to help develop alternative ZIKV vaccines, including mRNA-based and live-attenuated vaccines.
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