Synthesis of a dendritic cell-targeted self-assembled polymeric nanoparticle for selective delivery of mRNA vaccines to elicit enhanced immune responses

Recent development of SARS-CoV-2 spike mRNA vaccines to control the pandemic is a breakthrough in the field of vaccine development. mRNA vaccines are generally formulated with lipid nanoparticles (LNPs) which are composed of several lipids with specific ratios; however, they generally lack selective...

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Published inChemical science (Cambridge) Vol. 15; no. 29; pp. 11626 - 11632
Main Authors Fan, Chen-Yo, Wang, Szu-Wen, Chung, Cinya, Chen, Jia-Yan, Chang, Chia-Yen, Chen, Yu-Chen, Hsu, Tsui-Ling, Cheng, Ting-Jen R, Wong, Chi-Huey
Format Journal Article
LanguageEnglish
Published England Royal Society of Chemistry 24.07.2024
The Royal Society of Chemistry
Subjects
Chemical synthesis
Chemistry
Copolymers
Dendritic structure
Immune system
Lipids
Nanoparticles
Self-assembly
Vaccines
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Abstract Recent development of SARS-CoV-2 spike mRNA vaccines to control the pandemic is a breakthrough in the field of vaccine development. mRNA vaccines are generally formulated with lipid nanoparticles (LNPs) which are composed of several lipids with specific ratios; however, they generally lack selective delivery. To develop a selective delivery method for mRNA vaccine formulation, we reported here the synthesis of polymeric nanoparticles (PNPs) composed of a guanidine copolymer containing zwitterionic groups and a dendritic cell (DC)-targeted aryl-trimannoside ligand for encapsulation and selective delivery of an mRNA to dendritic cells. A DC-targeted SARS-CoV-2 spike mRNA-PNP vaccine was shown to elicit a stronger protective immune response in mice compared to the traditional mRNA-LNP vaccine and those without the selective delivery design. It is anticipated that this technology is generally applicable to other mRNA vaccines for DC-targeted delivery with enhanced immune response. Dendritic cell-targeted mRNA-PNP vaccines.
AbstractList Recent development of SARS-CoV-2 spike mRNA vaccines to control the pandemic is a breakthrough in the field of vaccine development. mRNA vaccines are generally formulated with lipid nanoparticles (LNPs) which are composed of several lipids with specific ratios; however, they generally lack selective delivery. To develop a selective delivery method for mRNA vaccine formulation, we reported here the synthesis of polymeric nanoparticles (PNPs) composed of a guanidine copolymer containing zwitterionic groups and a dendritic cell (DC)-targeted aryl-trimannoside ligand for encapsulation and selective delivery of an mRNA to dendritic cells. A DC-targeted SARS-CoV-2 spike mRNA-PNP vaccine was shown to elicit a stronger protective immune response in mice compared to the traditional mRNA-LNP vaccine and those without the selective delivery design. It is anticipated that this technology is generally applicable to other mRNA vaccines for DC-targeted delivery with enhanced immune response.Recent development of SARS-CoV-2 spike mRNA vaccines to control the pandemic is a breakthrough in the field of vaccine development. mRNA vaccines are generally formulated with lipid nanoparticles (LNPs) which are composed of several lipids with specific ratios; however, they generally lack selective delivery. To develop a selective delivery method for mRNA vaccine formulation, we reported here the synthesis of polymeric nanoparticles (PNPs) composed of a guanidine copolymer containing zwitterionic groups and a dendritic cell (DC)-targeted aryl-trimannoside ligand for encapsulation and selective delivery of an mRNA to dendritic cells. A DC-targeted SARS-CoV-2 spike mRNA-PNP vaccine was shown to elicit a stronger protective immune response in mice compared to the traditional mRNA-LNP vaccine and those without the selective delivery design. It is anticipated that this technology is generally applicable to other mRNA vaccines for DC-targeted delivery with enhanced immune response.
Recent development of SARS-CoV-2 spike mRNA vaccines to control the pandemic is a breakthrough in the field of vaccine development. mRNA vaccines are generally formulated with lipid nanoparticles (LNPs) which are composed of several lipids with specific ratios; however, they generally lack selective delivery. To develop a selective delivery method for mRNA vaccine formulation, we reported here the synthesis of polymeric nanoparticles (PNPs) composed of a guanidine copolymer containing zwitterionic groups and a dendritic cell (DC)-targeted aryl-trimannoside ligand for encapsulation and selective delivery of an mRNA to dendritic cells. A DC-targeted SARS-CoV-2 spike mRNA–PNP vaccine was shown to elicit a stronger protective immune response in mice compared to the traditional mRNA–LNP vaccine and those without the selective delivery design. It is anticipated that this technology is generally applicable to other mRNA vaccines for DC-targeted delivery with enhanced immune response.
Recent development of SARS-CoV-2 spike mRNA vaccines to control the pandemic is a breakthrough in the field of vaccine development. mRNA vaccines are generally formulated with lipid nanoparticles (LNPs) which are composed of several lipids with specific ratios; however, they generally lack selective delivery. To develop a selective delivery method for mRNA vaccine formulation, we reported here the synthesis of polymeric nanoparticles (PNPs) composed of a guanidine copolymer containing zwitterionic groups and a dendritic cell (DC)-targeted aryl-trimannoside ligand for encapsulation and selective delivery of an mRNA to dendritic cells. A DC-targeted SARS-CoV-2 spike mRNA-PNP vaccine was shown to elicit a stronger protective immune response in mice compared to the traditional mRNA-LNP vaccine and those without the selective delivery design. It is anticipated that this technology is generally applicable to other mRNA vaccines for DC-targeted delivery with enhanced immune response. Dendritic cell-targeted mRNA-PNP vaccines.
Author Wang, Szu-Wen
Fan, Chen-Yo
Chung, Cinya
Cheng, Ting-Jen R
Chen, Jia-Yan
Chang, Chia-Yen
Wong, Chi-Huey
Hsu, Tsui-Ling
Chen, Yu-Chen
AuthorAffiliation Department of Chemistry
Genomics Research Center
The Scripps Research Institute
Academia Sinica
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Snippet Recent development of SARS-CoV-2 spike mRNA vaccines to control the pandemic is a breakthrough in the field of vaccine development. mRNA vaccines are generally...
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SubjectTerms Chemical synthesis
Chemistry
Copolymers
Dendritic structure
Immune system
Lipids
Nanoparticles
Self-assembly
Vaccines
Title Synthesis of a dendritic cell-targeted self-assembled polymeric nanoparticle for selective delivery of mRNA vaccines to elicit enhanced immune responses
URI https://www.ncbi.nlm.nih.gov/pubmed/39055027
https://www.proquest.com/docview/3084057644
https://www.proquest.com/docview/3084774217
https://pubmed.ncbi.nlm.nih.gov/PMC11268467
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