Cited by 53Mosquito-borne diseases and controlSARS-CoV-2 and COVID-19 ResearchViral Infections and Outbreaks Research

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

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Jagger, Brett W, Dowd, Kimberly A, Chen, Rita E, Desai, Pritesh, Foreman, Bryant, Burgomaster, Katherine E, Himansu, Sunny, Kong, Wing-Pui +3 more·2019·The Journal of Infectious Diseases

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.

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  • In several studies, maternal vaccination with mRNA-loaded LNPs prevented fetal Zika virus transmission in pregnant mice.

    “In several studies, maternal vaccination with mRNA-loaded LNPs prevented fetal Zika virus transmission in pregnant mice225,226 and protected mouse neonates from herpesvirus227 and group A and group B streptococci228.”

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Authors
Jagger, B. W., Dowd, K. A., Chen, R. E., Desai, P., Foreman, B., Burgomaster, K. E., Himansu, S., Kong, W.-P., Graham, B. S., Pierson, T. C., & Diamond, M. S.
Affiliations
  • Washington University in St. Louis (US)
  • National Institutes of Health (US)
  • Moderna Therapeutics (United States) (US)
Corresponding author
  • Jagger, Brett W
  • Diamond, Michael S
Venue
The Journal of Infectious Diseases
Published
2019-07-01
Volume
220
Issue
10
Pages
1577-1588
ISSN
  • 0022-1899 (ISSN-L)
  • 1537-6613
OpenAlex
W2979623595
Cited by
53
References
49
Citations by year
2026: 3 · 2025: 5 · 2024: 6 · 2023: 11 · 2022: 6 · 2021: 10 · 2020: 11 · 2019: 1
FWCI
6.45
Type
journal article
Language
en
Open access
Locations
  • The Journal of Infectious Diseases (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (R01 AI073755, R01 HD091218, T32 AI007172)
  • National Institute of Allergy and Infectious Diseases Intramural Research
  • Moderna
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Health Sciences › Medicine › Infectious Diseases › Viral Infections and Outbreaks Research
Keywords
Zika virus, nucleic acid vaccines, mRNA vaccines, DNA plasmid vaccine, congenital Zika infection, vertical transmission, pregnancy, antibody-dependent enhancement, long-lived plasma cells, memory B cells, neutralizing antibodies, type I interferon signaling, vaccine efficacy
MeSH terms
Zika Virus Infection, Zika Virus, Animals, Antibodies, Viral, B-Lymphocytes, Female, Mice, Inbred C57BL, Mice, Transgenic, Plasma Cells, Pregnancy, Viral Vaccines, Infectious Disease Transmission, Vertical, Vaccines, DNA, Antibodies, Neutralizing

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