Gastrointestinal Delivery of an mRNA Vaccine Using Immunostimulatory Polymeric Nanoparticles
Abstract mRNA vaccines can be translated into protein antigens, in vivo, to effectively induce humoral and cellular immunity against these proteins. While current mRNA vaccines have generated potent immune responses, the need for ultracold storage conditions (− 80 °C) and healthcare p...
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| Format: | Article |
| Language: | English |
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Springer International Publishing
2023
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| Online Access: | https://hdl.handle.net/1721.1/152274 |
| _version_ | 1826199371832623104 |
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| author | Kim, Hyunjoon Kirtane, Ameya R. Kim, Na Y. Rajesh, Netra U. Tang, Chaoyang Ishida, Keiko Hayward, Alison M. Langer, Robert Traverso, Giovanni |
| author2 | Koch Institute for Integrative Cancer Research at MIT |
| author_facet | Koch Institute for Integrative Cancer Research at MIT Kim, Hyunjoon Kirtane, Ameya R. Kim, Na Y. Rajesh, Netra U. Tang, Chaoyang Ishida, Keiko Hayward, Alison M. Langer, Robert Traverso, Giovanni |
| author_sort | Kim, Hyunjoon |
| collection | MIT |
| description | Abstract
mRNA vaccines can be translated into protein antigens, in vivo, to effectively induce humoral and cellular immunity against these proteins. While current mRNA vaccines have generated potent immune responses, the need for ultracold storage conditions (− 80 °C) and healthcare professionals to administer the vaccine through the parenteral route has somewhat limited their distribution in rural areas and developing countries. Overcoming these challenges stands to transform future deployment of mRNA vaccines. In this study, we developed an mRNA vaccine that can trigger a systemic immune response through administration via the gastrointestinal (GI) tract and is stable at 4 °C. A library of cationic branched poly(β-amino ester) (PBAE) polymers was synthesized and characterized, from which a polymer with high intracellular mRNA delivery efficiency and immune stimulation capacity was down-selected. mRNA vaccines made with the lead polymer-elicited cellular and humoral immunity in mice. Furthermore, lyophilization conditions of the formulation were optimized to enable storage under refrigeration. Our results suggest that PBAE nanoparticles are potent mRNA delivery platforms that can elicit B cell and T cell activation, including antigen-specific cellular and humoral responses. This system can serve as an easily administrable, potent oral mRNA vaccine.
Graphical Abstract |
| first_indexed | 2024-09-23T11:19:10Z |
| format | Article |
| id | mit-1721.1/152274 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:19:10Z |
| publishDate | 2023 |
| publisher | Springer International Publishing |
| record_format | dspace |
| spelling | mit-1721.1/1522742024-01-19T20:47:14Z Gastrointestinal Delivery of an mRNA Vaccine Using Immunostimulatory Polymeric Nanoparticles Kim, Hyunjoon Kirtane, Ameya R. Kim, Na Y. Rajesh, Netra U. Tang, Chaoyang Ishida, Keiko Hayward, Alison M. Langer, Robert Traverso, Giovanni Koch Institute for Integrative Cancer Research at MIT Massachusetts Institute of Technology. Division of Comparative Medicine Massachusetts Institute of Technology. Department of Chemical Engineering Massachusetts Institute of Technology. Department of Mechanical Engineering Abstract mRNA vaccines can be translated into protein antigens, in vivo, to effectively induce humoral and cellular immunity against these proteins. While current mRNA vaccines have generated potent immune responses, the need for ultracold storage conditions (− 80 °C) and healthcare professionals to administer the vaccine through the parenteral route has somewhat limited their distribution in rural areas and developing countries. Overcoming these challenges stands to transform future deployment of mRNA vaccines. In this study, we developed an mRNA vaccine that can trigger a systemic immune response through administration via the gastrointestinal (GI) tract and is stable at 4 °C. A library of cationic branched poly(β-amino ester) (PBAE) polymers was synthesized and characterized, from which a polymer with high intracellular mRNA delivery efficiency and immune stimulation capacity was down-selected. mRNA vaccines made with the lead polymer-elicited cellular and humoral immunity in mice. Furthermore, lyophilization conditions of the formulation were optimized to enable storage under refrigeration. Our results suggest that PBAE nanoparticles are potent mRNA delivery platforms that can elicit B cell and T cell activation, including antigen-specific cellular and humoral responses. This system can serve as an easily administrable, potent oral mRNA vaccine. Graphical Abstract 2023-09-27T18:31:08Z 2023-09-27T18:31:08Z 2023-08-17 2023-08-20T03:10:14Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/152274 The AAPS Journal. 2023 Aug 17;25(5):81 PUBLISHER_CC en https://doi.org/10.1208/s12248-023-00844-z Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ The Author(s) application/pdf Springer International Publishing Springer International Publishing |
| spellingShingle | Kim, Hyunjoon Kirtane, Ameya R. Kim, Na Y. Rajesh, Netra U. Tang, Chaoyang Ishida, Keiko Hayward, Alison M. Langer, Robert Traverso, Giovanni Gastrointestinal Delivery of an mRNA Vaccine Using Immunostimulatory Polymeric Nanoparticles |
| title | Gastrointestinal Delivery of an mRNA Vaccine Using Immunostimulatory Polymeric Nanoparticles |
| title_full | Gastrointestinal Delivery of an mRNA Vaccine Using Immunostimulatory Polymeric Nanoparticles |
| title_fullStr | Gastrointestinal Delivery of an mRNA Vaccine Using Immunostimulatory Polymeric Nanoparticles |
| title_full_unstemmed | Gastrointestinal Delivery of an mRNA Vaccine Using Immunostimulatory Polymeric Nanoparticles |
| title_short | Gastrointestinal Delivery of an mRNA Vaccine Using Immunostimulatory Polymeric Nanoparticles |
| title_sort | gastrointestinal delivery of an mrna vaccine using immunostimulatory polymeric nanoparticles |
| url | https://hdl.handle.net/1721.1/152274 |
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