DNA vaccination before conception protects Zika virus–exposed pregnant macaques against prolonged viremia and improves fetal outcomes

Science Translational Medicine
18 December 2019 Vol 11, Issue 523

DNA vaccination before conception protects Zika virus–exposed pregnant macaques against prolonged viremia and improves fetal outcomes
By Koen K. A. Van Rompay, Rebekah I. Keesler, Amir Ardeshir, Jennifer Watanabe, Jodie Usachenko, Anil Singapuri, Christina Cruzen, Eliza Bliss-Moreau, Ashley M. Murphy, JoAnn L. Yee, Helen Webster, Maria Dennis, Tulika Singh, Holly Heimsath, Danilo Lemos, Jackson Stuart, Kaitlyn M. Morabito, Bryant M. Foreman, Katherine E. Burgomaster, Amy T. Noe, Kimberly A. Dowd, Erin Ball, Kevin Woolard, Pietro Presicce, Suhas G. Kallapur, Sallie R. Permar, Kathryn E. Foulds, Lark L. Coffey, Theodore C. Pierson, Barney S. Graham

Science Translational Medicine18 Dec 2019 Restricted Access
Curbing congenital Zika virus infection
The impact on a developing fetus is one of the most pressing concerns for developing vaccines or treatments for Zika virus. To assess fetal protection, Van Rompay et al. immunized nonhuman primates with a DNA vaccine before conception and then performed multiple Zika virus challenges in the first few months of pregnancy. Compared to unvaccinated controls, vaccinated animals had reduced viremia in terms of both magnitude and duration. Early fetal loss and fetal pathology was accordingly reduced. These results show that Zika virus vaccines given to women of childbearing age may help prevent damaging sequelae in offspring.
Zika virus (ZIKV) infection of pregnant women is associated with congenital Zika syndrome (CZS) and no vaccine is available, although several are being tested in clinical trials. We tested the efficacy of ZIKV DNA vaccine VRC5283 in a rhesus macaque model of congenital ZIKV infection. Most animal vaccine experiments have a set pathogen exposure several weeks or months after vaccination. In the real world, people encounter pathogens years or decades after vaccination, or may be repeatedly exposed if the virus is endemic. To more accurately mimic how this vaccine would be used, we immunized macaques before conception and then exposed them repeatedly to ZIKV during early and mid-gestation. In comparison to unimmunized animals, vaccinated animals had a significant reduction in peak magnitude and duration of maternal viremia, early fetal loss, fetal infection, and placental and fetal brain pathology. Vaccine-induced neutralizing antibody titers on the day of first ZIKV exposure were negatively associated with the magnitude of maternal viremia, and the absence of prolonged viremia was associated with better fetal outcomes. These data support further clinical development of ZIKV vaccine strategies to protect against negative fetal outcomes.