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


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.

SUBMITTER: Van Rompay KKA 

PROVIDER: S-EPMC7093037 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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

Van Rompay Koen K A KKA   Keesler Rebekah I RI   Ardeshir Amir A   Watanabe Jennifer J   Usachenko Jodie J   Singapuri Anil A   Cruzen Christina C   Bliss-Moreau Eliza E   Murphy Ashley M AM   Yee JoAnn L JL   Webster Helen H   Dennis Maria M   Singh Tulika T   Heimsath Holly H   Lemos Danilo D   Stuart Jackson J   Morabito Kaitlyn M KM   Foreman Bryant M BM   Burgomaster Katherine E KE   Noe Amy T AT   Dowd Kimberly A KA   Ball Erin E   Woolard Kevin K   Presicce Pietro P   Kallapur Suhas G SG   Permar Sallie R SR   Foulds Kathryn E KE   Coffey Lark L LL   Pierson Theodore C TC   Graham Barney S BS  

Science translational medicine 20191201 523


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  ...[more]

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