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Intradermal delivery of a synthetic DNA vaccine protects macaques from Middle East respiratory syndrome coronavirus

Emerging coronaviruses from zoonotic reservoirs, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have been associated with human-to-human transmission and si...

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Autores principales: Patel, Ami, Reuschel, Emma L., Xu, Ziyang, Zaidi, Faraz I., Kim, Kevin Y., Scott, Dana P., Mendoza, Janess, Ramos, Stephanie, Stoltz, Regina, Feldmann, Friederike, Okumura, Atsushi, Meade-White, Kimberly, Haddock, Elaine, Thomas, Tina, Rosenke, Rebecca, Lovaglio, Jamie, Hanley, Patrick W., Saturday, Greg, Muthumani, Kar, Feldmann, Heinz, Humeau, Laurent M., Broderick, Kate E., Weiner, David B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262283/
https://www.ncbi.nlm.nih.gov/pubmed/33886507
http://dx.doi.org/10.1172/jci.insight.146082
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author Patel, Ami
Reuschel, Emma L.
Xu, Ziyang
Zaidi, Faraz I.
Kim, Kevin Y.
Scott, Dana P.
Mendoza, Janess
Ramos, Stephanie
Stoltz, Regina
Feldmann, Friederike
Okumura, Atsushi
Meade-White, Kimberly
Haddock, Elaine
Thomas, Tina
Rosenke, Rebecca
Lovaglio, Jamie
Hanley, Patrick W.
Saturday, Greg
Muthumani, Kar
Feldmann, Heinz
Humeau, Laurent M.
Broderick, Kate E.
Weiner, David B.
author_facet Patel, Ami
Reuschel, Emma L.
Xu, Ziyang
Zaidi, Faraz I.
Kim, Kevin Y.
Scott, Dana P.
Mendoza, Janess
Ramos, Stephanie
Stoltz, Regina
Feldmann, Friederike
Okumura, Atsushi
Meade-White, Kimberly
Haddock, Elaine
Thomas, Tina
Rosenke, Rebecca
Lovaglio, Jamie
Hanley, Patrick W.
Saturday, Greg
Muthumani, Kar
Feldmann, Heinz
Humeau, Laurent M.
Broderick, Kate E.
Weiner, David B.
author_sort Patel, Ami
collection PubMed
description Emerging coronaviruses from zoonotic reservoirs, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have been associated with human-to-human transmission and significant morbidity and mortality. Here, we study both intradermal and intramuscular 2-dose delivery regimens of an advanced synthetic DNA vaccine candidate encoding a full-length MERS-CoV spike (S) protein, which induced potent binding and neutralizing antibodies as well as cellular immune responses in rhesus macaques. In a MERS-CoV challenge, all immunized rhesus macaques exhibited reduced clinical symptoms, lowered viral lung load, and decreased severity of pathological signs of disease compared with controls. Intradermal vaccination was dose sparing and more effective in this model at protecting animals from disease. The data support the further study of this vaccine for preventing MERS-CoV infection and transmission, including investigation of such vaccines and simplified delivery routes against emerging coronaviruses.
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spelling pubmed-82622832021-07-13 Intradermal delivery of a synthetic DNA vaccine protects macaques from Middle East respiratory syndrome coronavirus Patel, Ami Reuschel, Emma L. Xu, Ziyang Zaidi, Faraz I. Kim, Kevin Y. Scott, Dana P. Mendoza, Janess Ramos, Stephanie Stoltz, Regina Feldmann, Friederike Okumura, Atsushi Meade-White, Kimberly Haddock, Elaine Thomas, Tina Rosenke, Rebecca Lovaglio, Jamie Hanley, Patrick W. Saturday, Greg Muthumani, Kar Feldmann, Heinz Humeau, Laurent M. Broderick, Kate E. Weiner, David B. JCI Insight Research Article Emerging coronaviruses from zoonotic reservoirs, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have been associated with human-to-human transmission and significant morbidity and mortality. Here, we study both intradermal and intramuscular 2-dose delivery regimens of an advanced synthetic DNA vaccine candidate encoding a full-length MERS-CoV spike (S) protein, which induced potent binding and neutralizing antibodies as well as cellular immune responses in rhesus macaques. In a MERS-CoV challenge, all immunized rhesus macaques exhibited reduced clinical symptoms, lowered viral lung load, and decreased severity of pathological signs of disease compared with controls. Intradermal vaccination was dose sparing and more effective in this model at protecting animals from disease. The data support the further study of this vaccine for preventing MERS-CoV infection and transmission, including investigation of such vaccines and simplified delivery routes against emerging coronaviruses. American Society for Clinical Investigation 2021-05-24 /pmc/articles/PMC8262283/ /pubmed/33886507 http://dx.doi.org/10.1172/jci.insight.146082 Text en © 2021 Patel et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Patel, Ami
Reuschel, Emma L.
Xu, Ziyang
Zaidi, Faraz I.
Kim, Kevin Y.
Scott, Dana P.
Mendoza, Janess
Ramos, Stephanie
Stoltz, Regina
Feldmann, Friederike
Okumura, Atsushi
Meade-White, Kimberly
Haddock, Elaine
Thomas, Tina
Rosenke, Rebecca
Lovaglio, Jamie
Hanley, Patrick W.
Saturday, Greg
Muthumani, Kar
Feldmann, Heinz
Humeau, Laurent M.
Broderick, Kate E.
Weiner, David B.
Intradermal delivery of a synthetic DNA vaccine protects macaques from Middle East respiratory syndrome coronavirus
title Intradermal delivery of a synthetic DNA vaccine protects macaques from Middle East respiratory syndrome coronavirus
title_full Intradermal delivery of a synthetic DNA vaccine protects macaques from Middle East respiratory syndrome coronavirus
title_fullStr Intradermal delivery of a synthetic DNA vaccine protects macaques from Middle East respiratory syndrome coronavirus
title_full_unstemmed Intradermal delivery of a synthetic DNA vaccine protects macaques from Middle East respiratory syndrome coronavirus
title_short Intradermal delivery of a synthetic DNA vaccine protects macaques from Middle East respiratory syndrome coronavirus
title_sort intradermal delivery of a synthetic dna vaccine protects macaques from middle east respiratory syndrome coronavirus
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262283/
https://www.ncbi.nlm.nih.gov/pubmed/33886507
http://dx.doi.org/10.1172/jci.insight.146082
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