Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination

A single, low-dose intradermal immunization with lipid-nanoparticle-encapsulated nucleoside-modified mRNA encoding the pre-membrane and envelope glycoproteins of Zika virus protects both mice and rhesus macaques against infection and elicits rapid and long-lasting neutralizing antibody responses. mR...

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Veröffentlicht in:Nature (London) Jg. 543; H. 7644; S. 248 - 251
Hauptverfasser: Pardi, Norbert, Hogan, Michael J., Pelc, Rebecca S., Muramatsu, Hiromi, Andersen, Hanne, DeMaso, Christina R., Dowd, Kimberly A., Sutherland, Laura L., Scearce, Richard M., Parks, Robert, Wagner, Wendeline, Granados, Alex, Greenhouse, Jack, Walker, Michelle, Willis, Elinor, Yu, Jae-Sung, McGee, Charles E., Sempowski, Gregory D., Mui, Barbara L., Tam, Ying K., Huang, Yan-Jang, Vanlandingham, Dana, Holmes, Veronica M., Balachandran, Harikrishnan, Sahu, Sujata, Lifton, Michelle, Higgs, Stephen, Hensley, Scott E., Madden, Thomas D., Hope, Michael J., Karikó, Katalin, Santra, Sampa, Graham, Barney S., Lewis, Mark G., Pierson, Theodore C., Haynes, Barton F., Weissman, Drew
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 09.03.2017
Nature Publishing Group
Schlagworte:
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631/250/590/2293
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Adenoviruses
Animals
Antibodies, Neutralizing - immunology
Antibodies, Viral - immunology
Antigens, Viral - genetics
Antigens, Viral - immunology
Dendritic cells
Deoxyribonucleic acid
DNA
Female
Glycoproteins
Glycoproteins - genetics
Glycoproteins - immunology
Guillain-Barre syndrome
Humanities and Social Sciences
Immunization
Infections
Injections, Intradermal
letter
Macaca mulatta - immunology
Macaca mulatta - virology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
multidisciplinary
Nanoparticles - administration & dosage
Nanoparticles - chemistry
Pandemics
Proteins
RNA Stability
RNA, Messenger - administration & dosage
RNA, Messenger - chemistry
RNA, Messenger - genetics
RNA, Viral - administration & dosage
RNA, Viral - chemistry
RNA, Viral - genetics
Science
Studies
Time Factors
Vaccination
Vaccines
Vector-borne diseases
Viral Envelope Proteins - genetics
Viral Envelope Proteins - immunology
Viral Vaccines - administration & dosage
Viral Vaccines - immunology
Zika virus
Zika Virus - chemistry
Zika Virus - genetics
Zika Virus - immunology
Zika Virus Infection - immunology
Zika Virus Infection - prevention & control
ISSN:0028-0836, 1476-4687
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Zusammenfassung:A single, low-dose intradermal immunization with lipid-nanoparticle-encapsulated nucleoside-modified mRNA encoding the pre-membrane and envelope glycoproteins of Zika virus protects both mice and rhesus macaques against infection and elicits rapid and long-lasting neutralizing antibody responses. mRNA vaccine beats Zika virus Public health efforts to combat Zika virus disease are hampered by lack of a safe and efficient vaccine. Drew Weissman and colleagues report the development of a candidate vaccine that is based on chemically stabilized messenger RNA (mRNA) that encodes the premembrane and envelope glycoproteins of the Zika virus. This mRNA is packaged into lipid nanoparticles that can be delivered intradermally. A single dose of the vaccine gave mice and rhesus macaques long-term immunity to the Zika virus. These findings pave the way for the development of candidate vaccines that could protect humans against Zika virus disease. Zika virus (ZIKV) has recently emerged as a pandemic associated with severe neuropathology in newborns and adults 1 . 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 2 , 3 . 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  μ g 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  μ g 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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These authors contributed equally to this work
ISSN:0028-0836
1476-4687
DOI:10.1038/nature21428