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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 adults(1). 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 versati...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344708/ https://www.ncbi.nlm.nih.gov/pubmed/28151488 http://dx.doi.org/10.1038/nature21428 |
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author | 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 |
author_facet | 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 |
author_sort | Pardi, Norbert |
collection | PubMed |
description | Zika virus (ZIKV) has recently emerged as an explosive pandemic associated with severe neuropathology in newborns and adults(1). 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 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 (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. |
format | Online Article Text |
id | pubmed-5344708 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
record_format | MEDLINE/PubMed |
spelling | pubmed-53447082017-08-02 Zika virus protection by a single low dose nucleoside modified mRNA vaccination 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 Nature Article Zika virus (ZIKV) has recently emerged as an explosive pandemic associated with severe neuropathology in newborns and adults(1). 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 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 (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. 2017-02-02 2017-03-09 /pmc/articles/PMC5344708/ /pubmed/28151488 http://dx.doi.org/10.1038/nature21428 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms Reprints and permissions information is available at www.nature.com/reprints |
spellingShingle | Article 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 Zika virus protection by a single low dose nucleoside modified mRNA vaccination |
title | Zika virus protection by a single low dose nucleoside modified mRNA vaccination |
title_full | Zika virus protection by a single low dose nucleoside modified mRNA vaccination |
title_fullStr | Zika virus protection by a single low dose nucleoside modified mRNA vaccination |
title_full_unstemmed | Zika virus protection by a single low dose nucleoside modified mRNA vaccination |
title_short | Zika virus protection by a single low dose nucleoside modified mRNA vaccination |
title_sort | zika virus protection by a single low dose nucleoside modified mrna vaccination |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344708/ https://www.ncbi.nlm.nih.gov/pubmed/28151488 http://dx.doi.org/10.1038/nature21428 |
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