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

Koen K.A. van Rompay, Rebekah I. Keesler, Amir Ardeshir, Jennifer Watanabe, Jodie Usachenko, Anil Singapuri, Christina Cruzen, Eliza Bliss-Moreau, Ashley M. Murphy, Jo Ann 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. NoeKimberly 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

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbereaay2736
JournalScience Translational Medicine
Volume11
Issue number523
DOIs
StatePublished - Dec 18 2019

ASJC Scopus subject areas

  • Medicine(all)

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    van Rompay, K. K. A., Keesler, R. I., Ardeshir, A., Watanabe, J., Usachenko, J., Singapuri, A., Cruzen, C., Bliss-Moreau, E., Murphy, A. M., Yee, J. A. L., Webster, H., Dennis, M., Singh, T., Heimsath, H., Lemos, D., Stuart, J., Morabito, K. M., Foreman, B. M., Burgomaster, K. E., ... Graham, B. S. (2019). DNA vaccination before conception protects Zika virus–exposed pregnant macaques against prolonged viremia and improves fetal outcomes. Science Translational Medicine, 11(523), [eaay2736]. https://doi.org/10.1126/scitranslmed.aay2736