Modified mRNA vaccines protect against zika virus infection
Open accessAbstract
The emergence of ZIKV infection has prompted a global effort to develop safe and effective vaccines. We engineered a lipid nanoparticle (LNP) encapsulated modified mRNA vaccine encoding wild-type or variant ZIKV structural genes and tested immunogenicity and protection in mice. Two doses of modified mRNA LNPs encoding prM-E genes that produced virus-like particles resulted in high neutralizing antibody titers (∼1/100,000) that protected against ZIKV infection and conferred sterilizing immunity. To offset a theoretical concern of ZIKV vaccines inducing antibodies that cross-react with the related dengue virus (DENV), we designed modified prM-E RNA encoding mutations destroying the conserved fusion-loop epitope in the E protein. This variant protected against ZIKV and diminished production of antibodies enhancing DENV infection in cells or mice. A modified mRNA vaccine can prevent ZIKV disease and be adapted to reduce the risk of sensitizing individuals to subsequent exposure to DENV, should this become a clinically relevant concern.
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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, 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 [12]
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Experimental — accuracy not yet measuredIn prior studies, mice vaccinated intramuscularly with LNP-formulated mRNA vaccines were protected against Zika virus challenge infections.
“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 [12]
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 [12]
In combination with LNPs, modified mRNA is now the basis for the separate mRNA vaccine platform that has been proven most successful based on an optimal immune response originating from the compromise between LNP adjuvant function and modified mRNA, allowing improved efficacy and safety.
“In combination with LNPs, modified mRNA is now the basis for the separate mRNA vaccine platform41,44 that has been proven as the most successful based on its optimal immune response originating from the compromise between LNP adjuvant function33 and modified mRNA, allowing improved efficacy and safety.”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [44]
Two 10 μg doses of the lipid nanoparticle-encapsulated modified prM-E mRNA delivered 21 days apart protected mice from a Zika challenge and diminished the production of dengue-enhancing antibodies.
“Two 10 µg doses of the LNP-encapsulated modified mRNA delivered 21 days apart protected mice from a Zika challenge and diminished the production of dengue-enhancing antibodies156.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [156]
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 [194]
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 [194]
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“This phenomenon could be relevant to ZIKV vaccination because DENV and ZIKV are related closely, and vaccinated subjects in or travelers to endemic areas could become exposed secondarily to DENV, which infects ~390 million people per year (Bhatt et al., 2013).”
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Self-citation
- Authors
- Richner, J. M., Himansu, S., Dowd, K. A., Butler, S. L., Salazar, V., Fox, J. M., Julander, J. G., Tang, W. W., Shresta, S., Pierson, T. C., Ciaramella, G., & Diamond, M. S.
- Affiliations
- Washington University in St. Louis (US)
- National Institutes of Health (US)
- Utah State University (US)
- La Jolla Institute for Immunology (US)
- Corresponding author
- Ciaramella, Giuseppe
- Diamond, Michael S.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2017-03
- Volume
- 168
- Issue
- 6
- Pages
- 1114-1125.e10
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC5388441
- OpenAlex
- W2587850379
- Cited by
- 909
- References
- 74
- Citations by year
- 2026: 29 · 2025: 81 · 2024: 82 · 2023: 95 · 2022: 114 · 2021: 149 · 2020: 108 · 2019: 82 · 2018: 90 · 2017: 77 · 2014: 1
- FWCI
- 91.31
- Type
- journal article
- Language
- en
- Update notices
- erratum (2017-03-23)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH-NIAID (R01 AI073755, R01 AI104972, P01 AI106695, R01 AI116813)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- Zika virus, mRNA vaccines, lipid nanoparticles, virus-like particles, neutralizing antibodies, sterilizing immunity, vaccine design, immunogenicity
- MeSH terms
- Zika Virus Infection, Zika Virus, Animals, Epitopes, Female, Lipids, Mice, Inbred BALB C, Mice, Inbred C57BL, RNA, Messenger, Viral Vaccines, Mice, Nanoparticles, Mice, 129 Strain
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