1. DNA vaccination before conception protects Zika virus–exposed pregnant macaques against prolonged viremia and improves fetal outcomes
- Author
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Van Rompay, Koen KA, Keesler, Rebekah I, Ardeshir, Amir, Watanabe, Jennifer, Usachenko, Jodie, Singapuri, Anil, Cruzen, Christina, Bliss-Moreau, Eliza, Murphy, Ashley M, Yee, JoAnn L, Webster, Helen, Dennis, Maria, Singh, Tulika, Heimsath, Holly, Lemos, Danilo, Stuart, Jackson, Morabito, Kaitlyn M, Foreman, Bryant M, Burgomaster, Katherine E, Noe, Amy T, Dowd, Kimberly A, Ball, Erin, Woolard, Kevin, Presicce, Pietro, Kallapur, Suhas G, Permar, Sallie R, Foulds, Kathryn E, Coffey, Lark L, Pierson, Theodore C, and Graham, Barney S
- Subjects
Reproductive Medicine ,Medical Microbiology ,Biomedical and Clinical Sciences ,Neurosciences ,Rare Diseases ,Emerging Infectious Diseases ,Pregnancy ,Orphan Drug ,Infectious Diseases ,Immunization ,Vector-Borne Diseases ,Pediatric ,Prevention ,Women's Health ,Perinatal Period - Conditions Originating in Perinatal Period ,Biodefense ,Vaccine Related ,3.4 Vaccines ,Infection ,Reproductive health and childbirth ,Good Health and Well Being ,Animals ,Antibodies ,Neutralizing ,Female ,Macaca mulatta ,Pregnancy Complications ,Infectious ,Vaccination ,Vaccines ,DNA ,Viremia ,Zika Virus ,Zika Virus Infection ,Biological Sciences ,Medical and Health Sciences ,Medical biotechnology ,Biomedical engineering - 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.
- Published
- 2019