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Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses
Adjuvants are critical for improving the quality and magnitude of adaptive immune responses to vaccination. Lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA vaccines have shown great efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the mechanism of act...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566475/ https://www.ncbi.nlm.nih.gov/pubmed/34852217 http://dx.doi.org/10.1016/j.immuni.2021.11.001 |
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author | Alameh, Mohamad-Gabriel Tombácz, István Bettini, Emily Lederer, Katlyn Ndeupen, Sonia Sittplangkoon, Chutamath Wilmore, Joel R. Gaudette, Brian T. Soliman, Ousamah Y. Pine, Matthew Hicks, Philip Manzoni, Tomaz B. Knox, James J. Johnson, John L. Laczkó, Dorottya Muramatsu, Hiromi Davis, Benjamin Meng, Wenzhao Rosenfeld, Aaron M. Strohmeier, Shirin Lin, Paulo J.C. Mui, Barbara L. Tam, Ying K. Karikó, Katalin Jacquet, Alain Krammer, Florian Bates, Paul Cancro, Michael P. Weissman, Drew Luning Prak, Eline T. Allman, David Igyártó, Botond Z. Locci, Michela Pardi, Norbert |
author_facet | Alameh, Mohamad-Gabriel Tombácz, István Bettini, Emily Lederer, Katlyn Ndeupen, Sonia Sittplangkoon, Chutamath Wilmore, Joel R. Gaudette, Brian T. Soliman, Ousamah Y. Pine, Matthew Hicks, Philip Manzoni, Tomaz B. Knox, James J. Johnson, John L. Laczkó, Dorottya Muramatsu, Hiromi Davis, Benjamin Meng, Wenzhao Rosenfeld, Aaron M. Strohmeier, Shirin Lin, Paulo J.C. Mui, Barbara L. Tam, Ying K. Karikó, Katalin Jacquet, Alain Krammer, Florian Bates, Paul Cancro, Michael P. Weissman, Drew Luning Prak, Eline T. Allman, David Igyártó, Botond Z. Locci, Michela Pardi, Norbert |
author_sort | Alameh, Mohamad-Gabriel |
collection | PubMed |
description | Adjuvants are critical for improving the quality and magnitude of adaptive immune responses to vaccination. Lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA vaccines have shown great efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the mechanism of action of this vaccine platform is not well-characterized. Using influenza virus and SARS-CoV-2 mRNA and protein subunit vaccines, we demonstrated that our LNP formulation has intrinsic adjuvant activity that promotes induction of strong T follicular helper cell, germinal center B cell, long-lived plasma cell, and memory B cell responses that are associated with durable and protective antibodies in mice. Comparative experiments demonstrated that this LNP formulation outperformed a widely used MF59-like adjuvant, AddaVax. The adjuvant activity of the LNP relies on the ionizable lipid component and on IL-6 cytokine induction but not on MyD88- or MAVS-dependent sensing of LNPs. Our study identified LNPs as a versatile adjuvant that enhances the efficacy of traditional and next-generation vaccine platforms. |
format | Online Article Text |
id | pubmed-8566475 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85664752021-11-04 Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses Alameh, Mohamad-Gabriel Tombácz, István Bettini, Emily Lederer, Katlyn Ndeupen, Sonia Sittplangkoon, Chutamath Wilmore, Joel R. Gaudette, Brian T. Soliman, Ousamah Y. Pine, Matthew Hicks, Philip Manzoni, Tomaz B. Knox, James J. Johnson, John L. Laczkó, Dorottya Muramatsu, Hiromi Davis, Benjamin Meng, Wenzhao Rosenfeld, Aaron M. Strohmeier, Shirin Lin, Paulo J.C. Mui, Barbara L. Tam, Ying K. Karikó, Katalin Jacquet, Alain Krammer, Florian Bates, Paul Cancro, Michael P. Weissman, Drew Luning Prak, Eline T. Allman, David Igyártó, Botond Z. Locci, Michela Pardi, Norbert Immunity Article Adjuvants are critical for improving the quality and magnitude of adaptive immune responses to vaccination. Lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA vaccines have shown great efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the mechanism of action of this vaccine platform is not well-characterized. Using influenza virus and SARS-CoV-2 mRNA and protein subunit vaccines, we demonstrated that our LNP formulation has intrinsic adjuvant activity that promotes induction of strong T follicular helper cell, germinal center B cell, long-lived plasma cell, and memory B cell responses that are associated with durable and protective antibodies in mice. Comparative experiments demonstrated that this LNP formulation outperformed a widely used MF59-like adjuvant, AddaVax. The adjuvant activity of the LNP relies on the ionizable lipid component and on IL-6 cytokine induction but not on MyD88- or MAVS-dependent sensing of LNPs. Our study identified LNPs as a versatile adjuvant that enhances the efficacy of traditional and next-generation vaccine platforms. Elsevier Inc. 2021-12-14 2021-11-04 /pmc/articles/PMC8566475/ /pubmed/34852217 http://dx.doi.org/10.1016/j.immuni.2021.11.001 Text en © 2021 Elsevier Inc. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article Alameh, Mohamad-Gabriel Tombácz, István Bettini, Emily Lederer, Katlyn Ndeupen, Sonia Sittplangkoon, Chutamath Wilmore, Joel R. Gaudette, Brian T. Soliman, Ousamah Y. Pine, Matthew Hicks, Philip Manzoni, Tomaz B. Knox, James J. Johnson, John L. Laczkó, Dorottya Muramatsu, Hiromi Davis, Benjamin Meng, Wenzhao Rosenfeld, Aaron M. Strohmeier, Shirin Lin, Paulo J.C. Mui, Barbara L. Tam, Ying K. Karikó, Katalin Jacquet, Alain Krammer, Florian Bates, Paul Cancro, Michael P. Weissman, Drew Luning Prak, Eline T. Allman, David Igyártó, Botond Z. Locci, Michela Pardi, Norbert Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses |
title | Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses |
title_full | Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses |
title_fullStr | Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses |
title_full_unstemmed | Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses |
title_short | Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses |
title_sort | lipid nanoparticles enhance the efficacy of mrna and protein subunit vaccines by inducing robust t follicular helper cell and humoral responses |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566475/ https://www.ncbi.nlm.nih.gov/pubmed/34852217 http://dx.doi.org/10.1016/j.immuni.2021.11.001 |
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