Development of multivalent mRNA vaccine candidates for seasonal or pandemic influenza
Abstract 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 acceler...
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2021-12-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-021-00420-6 |
| _version_ | 1797431163565899776 |
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| author | Sudha Chivukula Timothy Plitnik Timothy Tibbitts Shrirang Karve Anusha Dias Donghui Zhang Rebecca Goldman Hardip Gopani Asad Khanmohammed Ashish Sarode Dustin Cooper Heesik Yoon Younghoon Kim Yanhua Yan Sophia T. Mundle Rachel Groppo Adrien Beauvais Jinrong Zhang Natalie G. Anosova Charles Lai Lu Li Gregory Ulinski Peter Piepenhagen Joshua DiNapoli Kirill V. Kalnin Victoria Landolfi Ron Swearingen Tong-Ming Fu Frank DeRosa Danilo Casimiro |
| author_facet | Sudha Chivukula Timothy Plitnik Timothy Tibbitts Shrirang Karve Anusha Dias Donghui Zhang Rebecca Goldman Hardip Gopani Asad Khanmohammed Ashish Sarode Dustin Cooper Heesik Yoon Younghoon Kim Yanhua Yan Sophia T. Mundle Rachel Groppo Adrien Beauvais Jinrong Zhang Natalie G. Anosova Charles Lai Lu Li Gregory Ulinski Peter Piepenhagen Joshua DiNapoli Kirill V. Kalnin Victoria Landolfi Ron Swearingen Tong-Ming Fu Frank DeRosa Danilo Casimiro |
| author_sort | Sudha Chivukula |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-09T09:38:02Z |
| format | Article |
| id | doaj.art-a7de43f864854e63ba72ae5665205ec9 |
| institution | Directory Open Access Journal |
| issn | 2059-0105 |
| language | English |
| last_indexed | 2024-03-09T09:38:02Z |
| publishDate | 2021-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj.art-a7de43f864854e63ba72ae5665205ec92023-12-02T01:10:41ZengNature Portfolionpj Vaccines2059-01052021-12-016111510.1038/s41541-021-00420-6Development of multivalent mRNA vaccine candidates for seasonal or pandemic influenzaSudha Chivukula0Timothy Plitnik1Timothy Tibbitts2Shrirang Karve3Anusha Dias4Donghui Zhang5Rebecca Goldman6Hardip Gopani7Asad Khanmohammed8Ashish Sarode9Dustin Cooper10Heesik Yoon11Younghoon Kim12Yanhua Yan13Sophia T. Mundle14Rachel Groppo15Adrien Beauvais16Jinrong Zhang17Natalie G. Anosova18Charles Lai19Lu Li20Gregory Ulinski21Peter Piepenhagen22Joshua DiNapoli23Kirill V. Kalnin24Victoria Landolfi25Ron Swearingen26Tong-Ming Fu27Frank DeRosa28Danilo Casimiro29Sanofi PasteurEmergent BiosolutionsSanofi PasteurTranslate Bio, a Sanofi CompanyTranslate Bio, a Sanofi CompanySanofi PasteurTranslate Bio, a Sanofi CompanyTranslate Bio, a Sanofi CompanyTranslate Bio, a Sanofi CompanyTranslate Bio, a Sanofi CompanyTranslate Bio, a Sanofi CompanySanofi PasteurSanofi PasteurSanofi PasteurSanofi PasteurPioneering MedicinesSanofi PasteurSeqirus IncSanofi PasteurSanofi PasteurSanofi PasteurSanofiSanofiSanofi PasteurEmergent BiosolutionsSanofi PasteurTranslate Bio, a Sanofi CompanyTexas Therapeutics Institute, The University of Texas Health Science Center at HoustonTranslate Bio, a Sanofi CompanySanofi PasteurAbstract 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.https://doi.org/10.1038/s41541-021-00420-6 |
| spellingShingle | Sudha Chivukula Timothy Plitnik Timothy Tibbitts Shrirang Karve Anusha Dias Donghui Zhang Rebecca Goldman Hardip Gopani Asad Khanmohammed Ashish Sarode Dustin Cooper Heesik Yoon Younghoon Kim Yanhua Yan Sophia T. Mundle Rachel Groppo Adrien Beauvais Jinrong Zhang Natalie G. Anosova Charles Lai Lu Li Gregory Ulinski Peter Piepenhagen Joshua DiNapoli Kirill V. Kalnin Victoria Landolfi Ron Swearingen Tong-Ming Fu Frank DeRosa Danilo Casimiro Development of multivalent mRNA vaccine candidates for seasonal or pandemic influenza npj Vaccines |
| 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 |
| url | https://doi.org/10.1038/s41541-021-00420-6 |
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