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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
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.
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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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