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Cell. 2017 Jul 13;170(2):273-283.e12. doi: 10.1016/j.cell.2017.06.040.

Vaccine Mediated Protection Against Zika Virus-Induced Congenital Disease.

Author information

1
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
2
Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
3
Viral Pathogenesis Section, Laboratory of Viral Diseases, National Institutes of Health, Bethesda, MD USA.
4
Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA.
5
Valera LLC, a Moderna Venture, 500 Technology Square, Cambridge, MA, USA.
6
Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA; Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Pará State, Brazil.
7
Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.
8
Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.
9
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX, USA.
10
Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA; Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX, USA.
11
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA; Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX, USA.
12
Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Pará State, Brazil; Department of Pathology, Pará State University, Belém, Brazil.
13
Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.
14
Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
15
Viral Pathogenesis Section, Laboratory of Viral Diseases, National Institutes of Health, Bethesda, MD USA. Electronic address: piersontc@niaid.nih.gov.
16
Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA; Institute for Translational Science, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA; Department of Pharmacology & Toxicology, University of Texas Medical Branch, Galveston, TX, USA; Sealy Center for Structural Biology & Molecular Biophysics, University of Texas Medical Branch, Galveston, TX, USA. Electronic address: peshi@utmb.edu.
17
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: diamond@wusm.wustl.edu.

Abstract

The emergence of Zika virus (ZIKV) and its association with congenital malformations has prompted the rapid development of vaccines. Although efficacy with multiple viral vaccine platforms has been established in animals, no study has addressed protection during pregnancy. We tested in mice two vaccine platforms, a lipid nanoparticle-encapsulated modified mRNA vaccine encoding ZIKV prM and E genes and a live-attenuated ZIKV strain encoding an NS1 protein without glycosylation, for their ability to protect against transmission to the fetus. Vaccinated dams challenged with a heterologous ZIKV strain at embryo day 6 (E6) and evaluated at E13 showed markedly diminished levels of viral RNA in maternal, placental, and fetal tissues, which resulted in protection against placental damage and fetal demise. As modified mRNA and live-attenuated vaccine platforms can restrict in utero transmission of ZIKV in mice, their further development in humans to prevent congenital ZIKV syndrome is warranted.

KEYWORDS:

Vaccine; antibody; fetus; flavivirus; immunity; microcephaly; pregnancy; transmission

PMID:
28708997
PMCID:
PMC5546158
DOI:
10.1016/j.cell.2017.06.040
[Indexed for MEDLINE]
Free PMC Article

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