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J Infect Dis. 2019 Oct 8;220(10):1577-1588. doi: 10.1093/infdis/jiz338.

Protective Efficacy of Nucleic Acid Vaccines Against Transmission of Zika Virus During Pregnancy in Mice.

Author information

1
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
2
Viral Pathogenesis Section, Laboratory of Viral Diseases, National Institutes of Health, Bethesda, Maryland.
3
Moderna, Cambridge, Massachusetts.
4
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
5
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri.
6
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri.
7
The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, Missouri.

Abstract

Zika virus (ZIKV) caused an epidemic of congenital malformations in 2015-2016. Although many vaccine candidates have been generated, few have demonstrated efficacy against congenital ZIKV infection. Here, we evaluated lipid-encapsulated messenger RNA (mRNA) vaccines and a DNA plasmid vaccine encoding the prM-E genes of ZIKV in mouse models of congenital infection. Although the DNA vaccine provided comparable efficacy against vertical transmission of ZIKV, the mRNA vaccines, including one that minimizes antibody-dependent enhancement of infection, elicited higher levels of antigen-specific long-lived plasma cells and memory B cells. Despite the induction of robust neutralizing antibody titers by all vaccines, breakthrough seeding of the placenta and fetal head was observed in a small subset of type I interferon signaling-deficient immunocompromised dams. In comparison, evaluation of one of the mRNA vaccines in a human STAT2-knockin transgenic immunocompetent mouse showed complete protection against congenital ZIKV transmission. These data will inform ongoing human ZIKV vaccine development efforts and enhance our understanding of the correlates of vaccine-induced protection.

KEYWORDS:

Zika; congenital Zika syndrome; neutralizing antibody; pregnancy; vaccine

PMID:
31260518
PMCID:
PMC6782106
[Available on 2020-10-08]
DOI:
10.1093/infdis/jiz338

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