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

Zika virus (ZIKV) has recently emerged as an explosive pandemic associated with severe neuropathology in newborns and adults1. There are no ZIKV-specific treatments or preventatives; thus, development of a safe and effective vaccine is a high priority. Messenger RNA (mRNA) has emerged as a versatile... Full description

Journal Title: Pardi N., M. J. Hogan, R. S. Pelc, H. Muramatsu, H. Andersen, C. R. DeMaso, K. A. Dowd, et al. 2017. “Zika virus protection by a single low dose nucleoside modified mRNA vaccination.” Nature 543 (7644): 248-251. doi:10.1038/nature21428. http://dx.doi.org/10.1038/nature21428.
Main Author: Pardi, Norbert
Other Authors: 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: Electronic Article Electronic Article
Language: English
Subjects:
ID: DOI: 10.1038/nature21428
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recordid: dash1/34375205
title: Zika virus protection by a single low dose nucleoside modified mRNA vaccination
format: Article
creator:
  • 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
subjects:
  • RNA, Messenger -- Administration & Dosage
  • Viral Vaccines -- Immunology
  • Zika Virus -- Immunology
  • Zika Virus Infection -- Prevention & Control
ispartof: Pardi, N., M. J. Hogan, R. S. Pelc, H. Muramatsu, H. Andersen, C. R. DeMaso, K. A. Dowd, et al. 2017. “Zika virus protection by a single low dose nucleoside modified mRNA vaccination.” Nature 543 (7644): 248-251. doi:10.1038/nature21428. http://dx.doi.org/10.1038/nature21428.
description: Zika virus (ZIKV) has recently emerged as an explosive pandemic associated with severe neuropathology in newborns and adults1. There are no ZIKV-specific treatments or preventatives; thus, 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 proteins2,3. 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 (prM-E) glycoproteins of a 2013 ZIKV outbreak strain elicited potent and durable neutralizing antibody responses in mice and non-human primates. Immunization with 30 μg of nucleoside-modified ZIKV mRNA-LNPs protected mice from ZIKV challenges at 2 weeks or 5 months post-vaccination, and a single dose of 50 μg was sufficient to protect non-human primates from a challenge at 5 weeks post-vaccination. These data demonstrate that nucleoside-modified mRNA-LNPs elicit rapid and durable protective immunity and thus represent a new and promising vaccine candidate for the global fight against ZIKV.
language: eng
source:
identifier: DOI: 10.1038/nature21428
fulltext: fulltext_linktorsrc
url: Link


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titleZika virus protection by a single low dose nucleoside modified mRNA vaccination
creatorPardi, 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
ispartofPardi, N., M. J. Hogan, R. S. Pelc, H. Muramatsu, H. Andersen, C. R. DeMaso, K. A. Dowd, et al. 2017. “Zika virus protection by a single low dose nucleoside modified mRNA vaccination.” Nature 543 (7644): 248-251. doi:10.1038/nature21428. http://dx.doi.org/10.1038/nature21428.
identifierDOI: 10.1038/nature21428
descriptionZika virus (ZIKV) has recently emerged as an explosive pandemic associated with severe neuropathology in newborns and adults1. There are no ZIKV-specific treatments or preventatives; thus, 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 proteins2,3. 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 (prM-E) glycoproteins of a 2013 ZIKV outbreak strain elicited potent and durable neutralizing antibody responses in mice and non-human primates. Immunization with 30 μg of nucleoside-modified ZIKV mRNA-LNPs protected mice from ZIKV challenges at 2 weeks or 5 months post-vaccination, and a single dose of 50 μg was sufficient to protect non-human primates from a challenge at 5 weeks post-vaccination. These data demonstrate that nucleoside-modified mRNA-LNPs elicit rapid and durable protective immunity and thus represent a new and promising vaccine candidate for the global fight against ZIKV.
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titleZika virus protection by a single low dose nucleoside modified mRNA vaccination
descriptionZika virus (ZIKV) has recently emerged as an explosive pandemic associated with severe neuropathology in newborns and adults1. There are no ZIKV-specific treatments or preventatives; thus, 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 proteins2,3. 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 (prM-E) glycoproteins of a 2013 ZIKV outbreak strain elicited potent and durable neutralizing antibody responses in mice and non-human primates. Immunization with 30 μg of nucleoside-modified ZIKV mRNA-LNPs protected mice from ZIKV challenges at 2 weeks or 5 months post-vaccination, and a single dose of 50 μg was sufficient to protect non-human primates from a challenge at 5 weeks post-vaccination. These data demonstrate that nucleoside-modified mRNA-LNPs elicit rapid and durable protective immunity and thus represent a new and promising vaccine candidate for the global fight against ZIKV.
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authorPardi, 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
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abstractZika virus (ZIKV) has recently emerged as an explosive pandemic associated with severe neuropathology in newborns and adults1. There are no ZIKV-specific treatments or preventatives; thus, 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 proteins2,3. 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 (prM-E) glycoproteins of a 2013 ZIKV outbreak strain elicited potent and durable neutralizing antibody responses in mice and non-human primates. Immunization with 30 μg of nucleoside-modified ZIKV mRNA-LNPs protected mice from ZIKV challenges at 2 weeks or 5 months post-vaccination, and a single dose of 50 μg was sufficient to protect non-human primates from a challenge at 5 weeks post-vaccination. These data demonstrate that nucleoside-modified mRNA-LNPs elicit rapid and durable protective immunity and thus represent a new and promising vaccine candidate for the global fight against ZIKV.
doi10.1038/nature21428
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