Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 220, Issue 10, Pages 1577-1588Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiz338
Keywords
Zika; vaccine; pregnancy; congenital Zika syndrome; vaccine; neutralizing antibody
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Funding
- National Institutes of Health (NIH) [R01 AI073755, R01 HD091218, T32 AI007172]
- National Institute of Allergy and Infectious Diseases Intramural Research Program
- Moderna
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [ZIAAI005128, ZIAAI001209] Funding Source: NIH RePORTER
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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.
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