Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination
Open accessAbstract
Zika virus (ZIKV) has recently emerged as a pandemic associated with severe neuropathology in newborns and adults. There are no ZIKV-specific treatments or preventatives. Therefore, the development of a safe and effective vaccine is a high priority. Messenger RNA (mRNA) has emerged as a versatile and highly effective platform to deliver vaccine antigens and therapeutic proteins. Here we demonstrate that a single low-dose intradermal immunization with lipid-nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP) encoding the pre-membrane and envelope glycoproteins of a strain from the ZIKV outbreak in 2013 elicited potent and durable neutralizing antibody responses in mice and non-human primates. Immunization with 30 μg of nucleoside-modified ZIKV mRNA-LNP protected mice against ZIKV challenges at 2 weeks or 5 months after vaccination, and a single dose of 50 μg was sufficient to protect non-human primates against a challenge at 5 weeks after vaccination. These data demonstrate that nucleoside-modified mRNA-LNP elicits rapid and durable protective immunity and therefore represents a new and promising vaccine candidate for the global fight against ZIKV.
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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 [14]
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 measuredNon-replicating mRNA is able to induce antibody titers in non-human primates.
“The study by Pardi et al. demonstrates that non-replicating mRNA is able to induce antibody titers in NHPs.”
From Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines (2017) · cites this paper as [14]
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 [14]
Protective efficacy against Zika virus challenge infections was demonstrated in non-human primates after intradermal vaccination.
“Importantly, protective efficacy against Zika virus challenge infections was also demonstrated in non-human primates (NHPs) after i.d. vaccination.14”
From Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines (2017) · cites this paper as [14]
Purification of IVT mRNA using cellulose, HPLC, FPLC, oligo(dT) purification, or TFF can further improve mRNA quality.
“Further improvement of mRNA quality can be made with purification of IVT mRNA using cellulose,39 high-pressure liquid chromatography (HPLC),40 fast protein liquid chromatography (FPLC),41 oligo(dT) purification,3 or tangential flow filtration (TFF).42,43”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [41]
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 [41]
A single 30 μg or 50 μg dose of a lipid nanoparticle-encapsulated nucleoside-modified prM-E mRNA protected mice and rhesus macaques, respectively, from a Zika challenge.
“One study showed that a single 30 µg or 50 µg dose of a LNP-encapsulated nucleoside-modified prM-E mRNA protected mice and rhesus macaques, respectively, from a Zika challenge153.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [153]
The neutralizing antibody titres generated by the mRNA vaccine were 50-100 times higher than those induced by purified inactivated virus and DNA vaccines in mice, and 50 times higher than a 1 mg DNA vaccine in macaques.
“Of note, the neutralizing antibody titres generated by the mRNA vaccine were 50–100 times higher than those induced by purified inactivated virus and DNA vaccines in mice, and 50 times higher than a 1 mg DNA vaccine in macaques153.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [153]
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 [192]
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Self-citation
- Authors
- Pardi, N., Hogan, M. J., Pelc, R. S., Muramatsu, H., Andersen, H., DeMaso, C. R., Dowd, K. A., Sutherland, L. L., Scearce, R. M., Parks, R., Wagner, W., Granados, A., Greenhouse, J., Walker, M., Willis, E., Yu, J.-S., McGee, C. E., Sempowski, G. D., Mui, B. L., Tam, Y. K., Huang, Y.-J., Vanlandingham, D., Holmes, V. M., Balachandran, H., Sahu, S., Lifton, M., Higgs, S., Hensley, S. E., Madden, T. D., Hope, M. J., Karikó, K., Santra, S., Graham, B. S., Lewis, M. G., Pierson, T. C., Haynes, B. F., & Weissman, D.
- Affiliations
- University of Pennsylvania (US)
- National Institutes of Health (US)
- Duke University (US)
- Bioqual (US)
- Acuitas Therapeutics (Canada) (CA)
- Kansas State University (US)
- Beth Israel Deaconess Medical Center (US)
- BioNTech (Germany) (DE)
- Corresponding author
- Weissman, Drew
- ORCID
- Pardi, Norbert
- Hogan, Michael J.
- Pelc, Rebecca S.
- Muramatsu, Hiromi
- DeMaso, Christina R.
- Dowd, Kimberly A.
- Sutherland, Laura L.
- Scearce, Richard M.
- Parks, Robert
- Greenhouse, Jack
- Willis, Elinor
- Sempowski, Gregory D.
- Mui, Barbara L.
- Tam, Ying K.
- Huang, Yan-Jang
- Vanlandingham, Dana
- Balachandran, Harikrishnan
- Lifton, Michelle
- Higgs, Stephen
- Hensley, Scott E.
- Karikó, Katalin
- Santra, Sampa
- Graham, Barney S.
- Lewis, Mark G.
- Pierson, Theodore C.
- Haynes, Barton F.
- Weissman, Drew
- Venue
- Nature
- Published
- 2017-02-02
- Volume
- 543
- Issue
- 7644
- Pages
- 248-251
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5344708
- OpenAlex
- W2584249987
- Cited by
- 884
- References
- 31
- Citations by year
- 2026: 33 · 2025: 75 · 2024: 80 · 2023: 91 · 2022: 101 · 2021: 151 · 2020: 104 · 2019: 62 · 2018: 98 · 2017: 89
- FWCI
- 90.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- University of Pennsylvania
- Vaccine Research Center
- National Institutes of Health (R01-AI084860, AI084860, NIH T32, NIH-R01, AI057229, AI-100645)
- College of Veterinary Medicine, Kansas State University
- National Institute of Allergy and Infectious Diseases (AI 057229, R01AI041860, AI-100645, AI007632, UM1AI100645, R01-AI084860, R01AI050484, T32AI007632, R01AI124429, AI058607, UC6AI058607, AI124429, R01AI090788, T32AI055428, T32AI070077, U19AI057229)
- NHLBI Division of Intramural Research
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Keywords
- Zika virus, mRNA vaccines, nucleoside-modified mRNA, lipid nanoparticles, intradermal vaccination, single-dose vaccination, neutralizing antibodies, vaccine protection, rhesus monkeys, mice
- MeSH terms
- Zika Virus Infection, Zika Virus, Animals, Antibodies, Viral, Antigens, Viral, Female, Glycoproteins, Injections, Intradermal, Macaca mulatta, Mice, Inbred BALB C, Mice, Inbred C57BL, RNA, Messenger, RNA, Viral, Time Factors, Vaccination, Viral Envelope Proteins, Viral Vaccines, RNA Stability, Mice, Nanoparticles, Antibodies, Neutralizing
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