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Development of multivalent mRNA vaccine candidates for seasonal or pandemic influenza
Recent approval of mRNA vaccines for emergency use against COVID-19 is likely to promote rapid development of mRNA-based vaccines targeting a wide range of infectious diseases. Compared to conventional approaches, this vaccine modality promises comparable potency while substantially accelerating the...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8677760/ https://www.ncbi.nlm.nih.gov/pubmed/34916519 http://dx.doi.org/10.1038/s41541-021-00420-6 |
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author | Chivukula, Sudha Plitnik, Timothy Tibbitts, Timothy Karve, Shrirang Dias, Anusha Zhang, Donghui Goldman, Rebecca Gopani, Hardip Khanmohammed, Asad Sarode, Ashish Cooper, Dustin Yoon, Heesik Kim, Younghoon Yan, Yanhua Mundle, Sophia T. Groppo, Rachel Beauvais, Adrien Zhang, Jinrong Anosova, Natalie G. Lai, Charles Li, Lu Ulinski, Gregory Piepenhagen, Peter DiNapoli, Joshua Kalnin, Kirill V. Landolfi, Victoria Swearingen, Ron Fu, Tong-Ming DeRosa, Frank Casimiro, Danilo |
author_facet | Chivukula, Sudha Plitnik, Timothy Tibbitts, Timothy Karve, Shrirang Dias, Anusha Zhang, Donghui Goldman, Rebecca Gopani, Hardip Khanmohammed, Asad Sarode, Ashish Cooper, Dustin Yoon, Heesik Kim, Younghoon Yan, Yanhua Mundle, Sophia T. Groppo, Rachel Beauvais, Adrien Zhang, Jinrong Anosova, Natalie G. Lai, Charles Li, Lu Ulinski, Gregory Piepenhagen, Peter DiNapoli, Joshua Kalnin, Kirill V. Landolfi, Victoria Swearingen, Ron Fu, Tong-Ming DeRosa, Frank Casimiro, Danilo |
author_sort | Chivukula, Sudha |
collection | PubMed |
description | Recent approval of mRNA vaccines for emergency use against COVID-19 is likely to promote rapid development of mRNA-based vaccines targeting a wide range of infectious diseases. Compared to conventional approaches, this vaccine modality promises comparable potency while substantially accelerating the pace of development and deployment of vaccine doses. Already demonstrated successfully for single antigen vaccines such as for COVID-19, this technology could be optimized for complex multi-antigen vaccines. Herein, utilizing multiple influenza antigens, we demonstrated the suitability of the mRNA therapeutic (MRT) platform for such applications. Seasonal influenza vaccines have three or four hemagglutinin (HA) antigens of different viral subtypes. In addition, influenza neuraminidase (NA), a tetrameric membrane protein, is identified as an antigen that has been linked to protective immunity against severe viral disease. We detail the efforts in optimizing formulations of influenza candidates that use unmodified mRNA encoding full-length HA or full-length NA encapsulated in lipid nanoparticles (LNPs). HA and NA mRNA-LNP formulations, either as monovalent or as multivalent vaccines, induced strong functional antibody and cellular responses in non-human primates and such antigen-specific antibody responses were associated with protective efficacy against viral challenge in mice. |
format | Online Article Text |
id | pubmed-8677760 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-86777602022-01-04 Development of multivalent mRNA vaccine candidates for seasonal or pandemic influenza Chivukula, Sudha Plitnik, Timothy Tibbitts, Timothy Karve, Shrirang Dias, Anusha Zhang, Donghui Goldman, Rebecca Gopani, Hardip Khanmohammed, Asad Sarode, Ashish Cooper, Dustin Yoon, Heesik Kim, Younghoon Yan, Yanhua Mundle, Sophia T. Groppo, Rachel Beauvais, Adrien Zhang, Jinrong Anosova, Natalie G. Lai, Charles Li, Lu Ulinski, Gregory Piepenhagen, Peter DiNapoli, Joshua Kalnin, Kirill V. Landolfi, Victoria Swearingen, Ron Fu, Tong-Ming DeRosa, Frank Casimiro, Danilo NPJ Vaccines Article Recent approval of mRNA vaccines for emergency use against COVID-19 is likely to promote rapid development of mRNA-based vaccines targeting a wide range of infectious diseases. Compared to conventional approaches, this vaccine modality promises comparable potency while substantially accelerating the pace of development and deployment of vaccine doses. Already demonstrated successfully for single antigen vaccines such as for COVID-19, this technology could be optimized for complex multi-antigen vaccines. Herein, utilizing multiple influenza antigens, we demonstrated the suitability of the mRNA therapeutic (MRT) platform for such applications. Seasonal influenza vaccines have three or four hemagglutinin (HA) antigens of different viral subtypes. In addition, influenza neuraminidase (NA), a tetrameric membrane protein, is identified as an antigen that has been linked to protective immunity against severe viral disease. We detail the efforts in optimizing formulations of influenza candidates that use unmodified mRNA encoding full-length HA or full-length NA encapsulated in lipid nanoparticles (LNPs). HA and NA mRNA-LNP formulations, either as monovalent or as multivalent vaccines, induced strong functional antibody and cellular responses in non-human primates and such antigen-specific antibody responses were associated with protective efficacy against viral challenge in mice. Nature Publishing Group UK 2021-12-16 /pmc/articles/PMC8677760/ /pubmed/34916519 http://dx.doi.org/10.1038/s41541-021-00420-6 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 Chivukula, Sudha Plitnik, Timothy Tibbitts, Timothy Karve, Shrirang Dias, Anusha Zhang, Donghui Goldman, Rebecca Gopani, Hardip Khanmohammed, Asad Sarode, Ashish Cooper, Dustin Yoon, Heesik Kim, Younghoon Yan, Yanhua Mundle, Sophia T. Groppo, Rachel Beauvais, Adrien Zhang, Jinrong Anosova, Natalie G. Lai, Charles Li, Lu Ulinski, Gregory Piepenhagen, Peter DiNapoli, Joshua Kalnin, Kirill V. Landolfi, Victoria Swearingen, Ron Fu, Tong-Ming DeRosa, Frank Casimiro, Danilo Development of multivalent mRNA vaccine candidates for seasonal or pandemic influenza |
title | Development of multivalent mRNA vaccine candidates for seasonal or pandemic influenza |
title_full | Development of multivalent mRNA vaccine candidates for seasonal or pandemic influenza |
title_fullStr | Development of multivalent mRNA vaccine candidates for seasonal or pandemic influenza |
title_full_unstemmed | Development of multivalent mRNA vaccine candidates for seasonal or pandemic influenza |
title_short | Development of multivalent mRNA vaccine candidates for seasonal or pandemic influenza |
title_sort | development of multivalent mrna vaccine candidates for seasonal or pandemic influenza |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8677760/ https://www.ncbi.nlm.nih.gov/pubmed/34916519 http://dx.doi.org/10.1038/s41541-021-00420-6 |
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