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SARS-CoV-2 protein subunit vaccination of mice and rhesus macaques elicits potent and durable neutralizing antibody responses

The outbreak and spread of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) is a current global health emergency, and effective prophylactic vaccines are needed urgently. The spike glycoprotein of SARS-CoV-2 mediates entry into host cells, and thus is the target of neutralizing antibodie...

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Autores principales: Mandolesi, Marco, Sheward, Daniel J., Hanke, Leo, Ma, Junjie, Pushparaj, Pradeepa, Perez Vidakovics, Laura, Kim, Changil, Àdori, Monika, Lenart, Klara, Loré, Karin, Castro Dopico, Xaquin, Coquet, Jonathan M., McInerney, Gerald M., Karlsson Hedestam, Gunilla B., Murrell, Ben
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020888/
https://www.ncbi.nlm.nih.gov/pubmed/33842900
http://dx.doi.org/10.1016/j.xcrm.2021.100252
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author Mandolesi, Marco
Sheward, Daniel J.
Hanke, Leo
Ma, Junjie
Pushparaj, Pradeepa
Perez Vidakovics, Laura
Kim, Changil
Àdori, Monika
Lenart, Klara
Loré, Karin
Castro Dopico, Xaquin
Coquet, Jonathan M.
McInerney, Gerald M.
Karlsson Hedestam, Gunilla B.
Murrell, Ben
author_facet Mandolesi, Marco
Sheward, Daniel J.
Hanke, Leo
Ma, Junjie
Pushparaj, Pradeepa
Perez Vidakovics, Laura
Kim, Changil
Àdori, Monika
Lenart, Klara
Loré, Karin
Castro Dopico, Xaquin
Coquet, Jonathan M.
McInerney, Gerald M.
Karlsson Hedestam, Gunilla B.
Murrell, Ben
author_sort Mandolesi, Marco
collection PubMed
description The outbreak and spread of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) is a current global health emergency, and effective prophylactic vaccines are needed urgently. The spike glycoprotein of SARS-CoV-2 mediates entry into host cells, and thus is the target of neutralizing antibodies. Here, we show that adjuvanted protein immunization with soluble SARS-CoV-2 spike trimers, stabilized in prefusion conformation, results in potent antibody responses in mice and rhesus macaques, with neutralizing antibody titers exceeding those typically measured in SARS-CoV-2 seropositive humans by more than one order of magnitude. Neutralizing antibody responses were observed after a single dose, with exceptionally high titers achieved after boosting. A follow-up to monitor the waning of the neutralizing antibody responses in rhesus macaques demonstrated durable responses that were maintained at high and stable levels at least 4 months after boosting. These data support the development of adjuvanted SARS-CoV-2 prefusion-stabilized spike protein subunit vaccines.
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spelling pubmed-80208882021-04-06 SARS-CoV-2 protein subunit vaccination of mice and rhesus macaques elicits potent and durable neutralizing antibody responses Mandolesi, Marco Sheward, Daniel J. Hanke, Leo Ma, Junjie Pushparaj, Pradeepa Perez Vidakovics, Laura Kim, Changil Àdori, Monika Lenart, Klara Loré, Karin Castro Dopico, Xaquin Coquet, Jonathan M. McInerney, Gerald M. Karlsson Hedestam, Gunilla B. Murrell, Ben Cell Rep Med Report The outbreak and spread of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) is a current global health emergency, and effective prophylactic vaccines are needed urgently. The spike glycoprotein of SARS-CoV-2 mediates entry into host cells, and thus is the target of neutralizing antibodies. Here, we show that adjuvanted protein immunization with soluble SARS-CoV-2 spike trimers, stabilized in prefusion conformation, results in potent antibody responses in mice and rhesus macaques, with neutralizing antibody titers exceeding those typically measured in SARS-CoV-2 seropositive humans by more than one order of magnitude. Neutralizing antibody responses were observed after a single dose, with exceptionally high titers achieved after boosting. A follow-up to monitor the waning of the neutralizing antibody responses in rhesus macaques demonstrated durable responses that were maintained at high and stable levels at least 4 months after boosting. These data support the development of adjuvanted SARS-CoV-2 prefusion-stabilized spike protein subunit vaccines. Elsevier 2021-04-05 /pmc/articles/PMC8020888/ /pubmed/33842900 http://dx.doi.org/10.1016/j.xcrm.2021.100252 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Report
Mandolesi, Marco
Sheward, Daniel J.
Hanke, Leo
Ma, Junjie
Pushparaj, Pradeepa
Perez Vidakovics, Laura
Kim, Changil
Àdori, Monika
Lenart, Klara
Loré, Karin
Castro Dopico, Xaquin
Coquet, Jonathan M.
McInerney, Gerald M.
Karlsson Hedestam, Gunilla B.
Murrell, Ben
SARS-CoV-2 protein subunit vaccination of mice and rhesus macaques elicits potent and durable neutralizing antibody responses
title SARS-CoV-2 protein subunit vaccination of mice and rhesus macaques elicits potent and durable neutralizing antibody responses
title_full SARS-CoV-2 protein subunit vaccination of mice and rhesus macaques elicits potent and durable neutralizing antibody responses
title_fullStr SARS-CoV-2 protein subunit vaccination of mice and rhesus macaques elicits potent and durable neutralizing antibody responses
title_full_unstemmed SARS-CoV-2 protein subunit vaccination of mice and rhesus macaques elicits potent and durable neutralizing antibody responses
title_short SARS-CoV-2 protein subunit vaccination of mice and rhesus macaques elicits potent and durable neutralizing antibody responses
title_sort sars-cov-2 protein subunit vaccination of mice and rhesus macaques elicits potent and durable neutralizing antibody responses
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020888/
https://www.ncbi.nlm.nih.gov/pubmed/33842900
http://dx.doi.org/10.1016/j.xcrm.2021.100252
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