tetano
Editor, Senior Moderator
NPJ Vaccines
. 2021 Dec 16;6(1):153.
doi: 10.1038/s41541-021-00420-6.
Development of multivalent mRNA vaccine candidates for seasonal or pandemic influenza
Sudha Chivukula[SUP] 1 [/SUP], Timothy Plitnik[SUP] 2 [/SUP], Timothy Tibbitts[SUP] 3 [/SUP], Shrirang Karve[SUP] 4 [/SUP], Anusha Dias[SUP] 4 [/SUP], Donghui Zhang[SUP] 5 [/SUP], Rebecca Goldman[SUP] 4 [/SUP], Hardip Gopani[SUP] 4 [/SUP], Asad Khanmohammed[SUP] 4 [/SUP], Ashish Sarode[SUP] 4 [/SUP], Dustin Cooper[SUP] 4 [/SUP], Heesik Yoon[SUP] 5 [/SUP], Younghoon Kim[SUP] 3 [/SUP], Yanhua Yan[SUP] 3 [/SUP], Sophia T Mundle[SUP] 3 [/SUP], Rachel Groppo[SUP] 6 [/SUP], Adrien Beauvais[SUP] 3 [/SUP], Jinrong Zhang[SUP] 7 [/SUP], Natalie G Anosova[SUP] 3 [/SUP], Charles Lai[SUP] 3 [/SUP], Lu Li[SUP] 3 [/SUP], Gregory Ulinski[SUP] 8 [/SUP], Peter Piepenhagen[SUP] 8 [/SUP], Joshua DiNapoli[SUP] 3 [/SUP], Kirill V Kalnin[SUP] 2 [/SUP], Victoria Landolfi[SUP] 9 [/SUP], Ron Swearingen[SUP] 4 [/SUP], Tong-Ming Fu[SUP] 10 [/SUP], Frank DeRosa[SUP] 4 [/SUP], Danilo Casimiro[SUP] 11 [/SUP]
Affiliations
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.
. 2021 Dec 16;6(1):153.
doi: 10.1038/s41541-021-00420-6.
Development of multivalent mRNA vaccine candidates for seasonal or pandemic influenza
Sudha Chivukula[SUP] 1 [/SUP], Timothy Plitnik[SUP] 2 [/SUP], Timothy Tibbitts[SUP] 3 [/SUP], Shrirang Karve[SUP] 4 [/SUP], Anusha Dias[SUP] 4 [/SUP], Donghui Zhang[SUP] 5 [/SUP], Rebecca Goldman[SUP] 4 [/SUP], Hardip Gopani[SUP] 4 [/SUP], Asad Khanmohammed[SUP] 4 [/SUP], Ashish Sarode[SUP] 4 [/SUP], Dustin Cooper[SUP] 4 [/SUP], Heesik Yoon[SUP] 5 [/SUP], Younghoon Kim[SUP] 3 [/SUP], Yanhua Yan[SUP] 3 [/SUP], Sophia T Mundle[SUP] 3 [/SUP], Rachel Groppo[SUP] 6 [/SUP], Adrien Beauvais[SUP] 3 [/SUP], Jinrong Zhang[SUP] 7 [/SUP], Natalie G Anosova[SUP] 3 [/SUP], Charles Lai[SUP] 3 [/SUP], Lu Li[SUP] 3 [/SUP], Gregory Ulinski[SUP] 8 [/SUP], Peter Piepenhagen[SUP] 8 [/SUP], Joshua DiNapoli[SUP] 3 [/SUP], Kirill V Kalnin[SUP] 2 [/SUP], Victoria Landolfi[SUP] 9 [/SUP], Ron Swearingen[SUP] 4 [/SUP], Tong-Ming Fu[SUP] 10 [/SUP], Frank DeRosa[SUP] 4 [/SUP], Danilo Casimiro[SUP] 11 [/SUP]
Affiliations
- PMID: 34916519
- DOI: 10.1038/s41541-021-00420-6
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.