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Sci Transl Med. 2019 Dec 18;11(523). pii: eaay2736. doi: 10.1126/scitranslmed.aay2736.

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

Author information

1
California National Primate Research Center, University of California, Davis, Davis, CA 95616, USA. kkvanrompay@ucdavis.edu bgraham@nih.gov.
2
Department of Pathology, Microbiology and Immunology, University of California, Davis, Davis, CA 95616, USA.
3
California National Primate Research Center, University of California, Davis, Davis, CA 95616, USA.
4
Department of Psychology, University of California, Davis, Davis, CA 95616, USA.
5
Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA.
6
Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
7
Laboratory of Viral Diseases, NIAID, NIH, Bethesda, MD 20892, USA.
8
Divisions of Neonatology and Developmental Biology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
9
Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA. kkvanrompay@ucdavis.edu bgraham@nih.gov.

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.

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