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Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine

The CVnCoV (CureVac) mRNA vaccine for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was recently evaluated in a phase 2b/3 efficacy trial in humans(1). CV2CoV is a second-generation mRNA vaccine containing non-modified nucleosides but with optimized non-coding regions and enhanced ant...

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Autores principales: Gebre, Makda S., Rauch, Susanne, Roth, Nicole, Yu, Jingyou, Chandrashekar, Abishek, Mercado, Noe B., He, Xuan, Liu, Jinyan, McMahan, Katherine, Martinot, Amanda, Martinez, David R., Giffin, Victoria, Hope, David, Patel, Shivani, Sellers, Daniel, Sanborn, Owen, Barrett, Julia, Liu, Xiaowen, Cole, Andrew C., Pessaint, Laurent, Valentin, Daniel, Flinchbaugh, Zack, Yalley-Ogunro, Jake, Muench, Jeanne, Brown, Renita, Cook, Anthony, Teow, Elyse, Andersen, Hanne, Lewis, Mark G., Boon, Adrianus C. M., Baric, Ralph S., Mueller, Stefan O., Petsch, Benjamin, Barouch, Dan H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8770133/
https://www.ncbi.nlm.nih.gov/pubmed/34794169
http://dx.doi.org/10.1038/s41586-021-04231-6
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author Gebre, Makda S.
Rauch, Susanne
Roth, Nicole
Yu, Jingyou
Chandrashekar, Abishek
Mercado, Noe B.
He, Xuan
Liu, Jinyan
McMahan, Katherine
Martinot, Amanda
Martinez, David R.
Giffin, Victoria
Hope, David
Patel, Shivani
Sellers, Daniel
Sanborn, Owen
Barrett, Julia
Liu, Xiaowen
Cole, Andrew C.
Pessaint, Laurent
Valentin, Daniel
Flinchbaugh, Zack
Yalley-Ogunro, Jake
Muench, Jeanne
Brown, Renita
Cook, Anthony
Teow, Elyse
Andersen, Hanne
Lewis, Mark G.
Boon, Adrianus C. M.
Baric, Ralph S.
Mueller, Stefan O.
Petsch, Benjamin
Barouch, Dan H.
author_facet Gebre, Makda S.
Rauch, Susanne
Roth, Nicole
Yu, Jingyou
Chandrashekar, Abishek
Mercado, Noe B.
He, Xuan
Liu, Jinyan
McMahan, Katherine
Martinot, Amanda
Martinez, David R.
Giffin, Victoria
Hope, David
Patel, Shivani
Sellers, Daniel
Sanborn, Owen
Barrett, Julia
Liu, Xiaowen
Cole, Andrew C.
Pessaint, Laurent
Valentin, Daniel
Flinchbaugh, Zack
Yalley-Ogunro, Jake
Muench, Jeanne
Brown, Renita
Cook, Anthony
Teow, Elyse
Andersen, Hanne
Lewis, Mark G.
Boon, Adrianus C. M.
Baric, Ralph S.
Mueller, Stefan O.
Petsch, Benjamin
Barouch, Dan H.
author_sort Gebre, Makda S.
collection PubMed
description The CVnCoV (CureVac) mRNA vaccine for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was recently evaluated in a phase 2b/3 efficacy trial in humans(1). CV2CoV is a second-generation mRNA vaccine containing non-modified nucleosides but with optimized non-coding regions and enhanced antigen expression. Here we report the results of a head-to-head comparison of the immunogenicity and protective efficacy of CVnCoV and CV2CoV in non-human primates. We immunized 18 cynomolgus macaques with two doses of 12 μg lipid nanoparticle-formulated CVnCoV or CV2CoV or with sham (n = 6 per group). Compared with CVnCoV, CV2CoV induced substantially higher titres of binding and neutralizing antibodies, memory B cell responses and T cell responses as well as more potent neutralizing antibody responses against SARS-CoV-2 variants, including the Delta variant. Moreover, CV2CoV was found to be comparably immunogenic to the BNT162b2 (Pfizer) vaccine in macaques. Although CVnCoV provided partial protection against SARS-CoV-2 challenge, CV2CoV afforded more robust protection with markedly lower viral loads in the upper and lower respiratory tracts. Binding and neutralizing antibody titres were correlated with protective efficacy. These data demonstrate that optimization of non-coding regions can greatly improve the immunogenicity and protective efficacy of a non-modified mRNA SARS-CoV-2 vaccine in non-human primates.
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spelling pubmed-87701332022-02-04 Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine Gebre, Makda S. Rauch, Susanne Roth, Nicole Yu, Jingyou Chandrashekar, Abishek Mercado, Noe B. He, Xuan Liu, Jinyan McMahan, Katherine Martinot, Amanda Martinez, David R. Giffin, Victoria Hope, David Patel, Shivani Sellers, Daniel Sanborn, Owen Barrett, Julia Liu, Xiaowen Cole, Andrew C. Pessaint, Laurent Valentin, Daniel Flinchbaugh, Zack Yalley-Ogunro, Jake Muench, Jeanne Brown, Renita Cook, Anthony Teow, Elyse Andersen, Hanne Lewis, Mark G. Boon, Adrianus C. M. Baric, Ralph S. Mueller, Stefan O. Petsch, Benjamin Barouch, Dan H. Nature Article The CVnCoV (CureVac) mRNA vaccine for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was recently evaluated in a phase 2b/3 efficacy trial in humans(1). CV2CoV is a second-generation mRNA vaccine containing non-modified nucleosides but with optimized non-coding regions and enhanced antigen expression. Here we report the results of a head-to-head comparison of the immunogenicity and protective efficacy of CVnCoV and CV2CoV in non-human primates. We immunized 18 cynomolgus macaques with two doses of 12 μg lipid nanoparticle-formulated CVnCoV or CV2CoV or with sham (n = 6 per group). Compared with CVnCoV, CV2CoV induced substantially higher titres of binding and neutralizing antibodies, memory B cell responses and T cell responses as well as more potent neutralizing antibody responses against SARS-CoV-2 variants, including the Delta variant. Moreover, CV2CoV was found to be comparably immunogenic to the BNT162b2 (Pfizer) vaccine in macaques. Although CVnCoV provided partial protection against SARS-CoV-2 challenge, CV2CoV afforded more robust protection with markedly lower viral loads in the upper and lower respiratory tracts. Binding and neutralizing antibody titres were correlated with protective efficacy. These data demonstrate that optimization of non-coding regions can greatly improve the immunogenicity and protective efficacy of a non-modified mRNA SARS-CoV-2 vaccine in non-human primates. Nature Publishing Group UK 2021-11-18 2022 /pmc/articles/PMC8770133/ /pubmed/34794169 http://dx.doi.org/10.1038/s41586-021-04231-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Gebre, Makda S.
Rauch, Susanne
Roth, Nicole
Yu, Jingyou
Chandrashekar, Abishek
Mercado, Noe B.
He, Xuan
Liu, Jinyan
McMahan, Katherine
Martinot, Amanda
Martinez, David R.
Giffin, Victoria
Hope, David
Patel, Shivani
Sellers, Daniel
Sanborn, Owen
Barrett, Julia
Liu, Xiaowen
Cole, Andrew C.
Pessaint, Laurent
Valentin, Daniel
Flinchbaugh, Zack
Yalley-Ogunro, Jake
Muench, Jeanne
Brown, Renita
Cook, Anthony
Teow, Elyse
Andersen, Hanne
Lewis, Mark G.
Boon, Adrianus C. M.
Baric, Ralph S.
Mueller, Stefan O.
Petsch, Benjamin
Barouch, Dan H.
Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine
title Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine
title_full Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine
title_fullStr Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine
title_full_unstemmed Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine
title_short Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine
title_sort optimization of non-coding regions for a non-modified mrna covid-19 vaccine
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8770133/
https://www.ncbi.nlm.nih.gov/pubmed/34794169
http://dx.doi.org/10.1038/s41586-021-04231-6
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