Gastrointestinal Delivery of an mRNA Vaccine Using Immunostimulatory Polymeric Nanoparticles
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12248_2023_Article_844.pdf
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Author(s)
Kim, Hyunjoon
Kirtane, Ameya R.
Kim, Na Y.
Rajesh, Netra U.
Tang, Chaoyang
Ishida, Keiko
Hayward, Alison M.
Langer, Robert
Traverso, Giovanni
Date Issued
August 17, 2023
Publisher
Springer International Publishing
Citation
The AAPS Journal. 2023 Aug 17;25(5):81
Version
Final published version
Abstract
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
MIT Department
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
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DOI of Published Version
https://doi.org/10.1208/s12248-023-00844-z
