Vaccine Mediated Protection Against Zika Virus-Induced Congenital Disease
Open accessAbstract
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.
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Chemically modified nucleosides have been used in recent publications to reach sufficient antigen expression.
“In recent publications chemically modified nucleosides were used to reach sufficient antigen expression,12–15 which is in contrast to our proprietary mRNA technology, which employs sequence optimization and selected untranslated regions (UTRs) to achieve high antigen expression.16”
From Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines (2017) · cites this paper as [13]
The Method Details section (page unavailable) confirms that the vaccine mRNA used a chemically modified nucleoside, substituting 1-methylpseudoUTP for UTP. It attributes increased translation efficiency to the cap structure, while the Discussion (page unavailable) says modified nucleosides were used to minimize innate immune activation; the paper does not establish that the nucleoside modification was used to reach sufficient antigen expression. (LLM, conf=0.85)
Experimental — accuracy not yet measuredRecent studies using chemically modified mRNA revealed protective efficacy of LNP-formulated mRNA vaccines for Zika virus after i.m. administration in mice or i.d. administration in NHPs, and immunogenicity for influenza HA strains H10N8 and H7N9 after i.m. administration in NHPs and humans.
“Recent studies using chemically modified mRNA revealed protective efficacy of LNP-formulated mRNA vaccines for Zika virus after i.m. administration in mice or i.d. administration in NHPs, as well as immunogenicity for influenza HA of the strains H10N8 and H7N9 after i.m. administration in NHPs and humans.12–15”
From Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines (2017) · cites this paper as [13]
Split into 2 atoms — 1 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredIn prior studies, mice vaccinated intramuscularly with LNP-formulated mRNA vaccines were protected against placental damage and fetal demise in challenged pregnant mice.
“In these studies, mice were vaccinated i.m. with LNP-formulated mRNA vaccines inducing protection against Zika virus challenge infections,12 and protection against placental damage and fetal demise in challenged pregnant mice.13”
From Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines (2017) · cites this paper as [13]
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.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [225]
The vaccine mRNA-1893 is a clinical candidate that contains lipid nanoparticles with mRNA encoding Zika virus premembrane and envelope (prM-E) proteins.
“The vaccine mRNA-1893 is a clinical candidate that contains lipid nanoparticles with mRNA encoding Zika virus premembrane and envelope (prM-E) proteins193,194.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [193]
Lipid nanoparticle-mRNA formulations are being explored for Zika virus vaccines.
“Lipid nanoparticle–mRNA formulations are further being explored for Zika virus vaccines38,190,192–194.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [193]
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“with LNP-formulated mRNA vaccines inducing protection against Zika virus challenge infections,(12) and protection against placental damage and fetal demise in challenged pregnant mice.(13) Importantly, protective efficacy against Zika virus challenge infections was also demonstrated in non-human primates (NHPs) after…”
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Self-citation
- Authors
- Richner, J. M., Jagger, B. W., Shan, C., Fontes, C. R., Dowd, K. A., Cao, B., Himansu, S., Caine, E. A., Nunes, B. T. D., Medeiros, D. B. A., Muruato, A. E., Foreman, B. M., Luo, H., Wang, T., Barrett, A. D., Weaver, S. C., Vasconcelos, P. F. C., Rossi, S. L., Ciaramella, G., Mysorekar, I. U., Pierson, T. C., Shi, P.-Y., & Diamond, M. S.
- Affiliations
- Washington University in St. Louis (US)
- The University of Texas Medical Branch at Galveston (US)
- National Institutes of Health (US)
- Ministério da Saúde (BR)
- Corresponding author
- Pierson, Theodore C.
- Shi, Pei-Yong
- Diamond, Michael S.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2017-07
- Volume
- 170
- Issue
- 2
- Pages
- 273-283.e12
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC5546158
- OpenAlex
- W2734414012
- Cited by
- 267
- References
- 52
- Citations by year
- 2026: 5 · 2025: 17 · 2024: 20 · 2023: 15 · 2022: 29 · 2021: 42 · 2020: 32 · 2019: 35 · 2018: 54 · 2017: 18
- FWCI
- 35.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH-NIAID (R01 AI073755, R01 AI104972, P01 AI106695, R24AI120942, T32 AI007172)
- NIH/NICHD (R01 HD091218)
- DARPA (# W911NF-13-1-0417)
- Burroughs Wellcome Fund (21-FY13-28)
- March of Dimes
- Moderna (OTM10991)
- University of Texas Medical Branch
- University of Texas
- Pan American Health Organization (SCON2016-01353)
- Ministry of Health of Brazil
- CNPq (303999/2016-0, 440405/2016-5)
- CAPES
- 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, congenital Zika syndrome, maternal immunization, in utero transmission, placental transmission, lipid nanoparticle vaccine, live attenuated vaccine, NS1 protein, fetal protection, pregnancy
- MeSH terms
- Zika Virus Infection, Zika Virus, Aedes, Animals, Antibodies, Viral, Blood Cells, Embryo, Mammalian, Female, Fetus, Humans, Lipids, Male, Mice, Inbred C57BL, Mutation, RNA, Messenger, Specific Pathogen-Free Organisms, Viral Vaccines, Viral Nonstructural Proteins, Vaccines, Subunit, Mice, Antibodies, Neutralizing
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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