Modified PEG-Lipids Enhance the Nasal Mucosal Immune Capacity of Lipid Nanoparticle mRNA Vaccines
Background/Objectives: Omicron, the predominant variant of SARS-CoV-2, exhibits strong immune-evasive properties, leading to the reduced efficacy of existing vaccines. Consequently, the development of versatile vaccines is imperative. Intranasal mRNA vaccines offer convenient administration and have...
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2024-11-01
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| author | Meng Li Jing Yi Yicheng Lu Ting Liu Haonan Xing Xiwei Wang Hui Zhang Nan Liu Zengming Wang Aiping Zheng |
| author_facet | Meng Li Jing Yi Yicheng Lu Ting Liu Haonan Xing Xiwei Wang Hui Zhang Nan Liu Zengming Wang Aiping Zheng |
| author_sort | Meng Li |
| collection | DOAJ |
| description | Background/Objectives: Omicron, the predominant variant of SARS-CoV-2, exhibits strong immune-evasive properties, leading to the reduced efficacy of existing vaccines. Consequently, the development of versatile vaccines is imperative. Intranasal mRNA vaccines offer convenient administration and have the potential to enhance mucosal immunity. However, delivering vaccines via the nasal mucosa requires overcoming complex physiological barriers. The aim of this study is to modify PEGylated lipids to enhance the mucosal immune efficacy of the vaccine. Methods: The PEGylated lipid component of lipid nanoparticle (LNP) delivery vectors was modified with chitosan or mannose to generate novel LNPs that enhance vaccine adhesion or targeting on mucosal surfaces. The impact of the mRNA encoding the receptor-binding domain of Omicron BA.4/BA.5 on the immune response was examined. Results: Compared to the unmodified LNP group, the IgG and IgA titers in the chitosan or mannose-modified LNP groups showed an increasing trend. The chitosan-modified group showed better effects. Notably, the PEGylated lipid with 1.5 mol% of chitosan modification produced high levels of IgG1 and IgG2a antibodies, promoting Th1/Th2 responses while also generating high levels of IgA, which can induce stronger cellular immunity, humoral immunity, and mucosal immunity. Conclusions: The 1.5 mol% of chitosan-modified LNPs (mRNA-LNP-1.5CS) can serve as a safe and effective carrier for intranasal mRNA vaccines, offering a promising strategy for combating the Omicron variant. |
| format | Article |
| id | doaj-art-f245da13c37a4ba287d34652c99feef3 |
| institution | Kabale University |
| issn | 1999-4923 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj-art-f245da13c37a4ba287d34652c99feef32024-11-26T18:17:55ZengMDPI AGPharmaceutics1999-49232024-11-011611142310.3390/pharmaceutics16111423Modified PEG-Lipids Enhance the Nasal Mucosal Immune Capacity of Lipid Nanoparticle mRNA VaccinesMeng Li0Jing Yi1Yicheng Lu2Ting Liu3Haonan Xing4Xiwei Wang5Hui Zhang6Nan Liu7Zengming Wang8Aiping Zheng9Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Haidian District, Beijing 100850, ChinaBeijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Haidian District, Beijing 100850, ChinaBeijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Haidian District, Beijing 100850, ChinaBeijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Haidian District, Beijing 100850, ChinaBeijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Haidian District, Beijing 100850, ChinaBeijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Haidian District, Beijing 100850, ChinaBeijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Haidian District, Beijing 100850, ChinaBeijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Haidian District, Beijing 100850, ChinaBeijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Haidian District, Beijing 100850, ChinaBeijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Haidian District, Beijing 100850, ChinaBackground/Objectives: Omicron, the predominant variant of SARS-CoV-2, exhibits strong immune-evasive properties, leading to the reduced efficacy of existing vaccines. Consequently, the development of versatile vaccines is imperative. Intranasal mRNA vaccines offer convenient administration and have the potential to enhance mucosal immunity. However, delivering vaccines via the nasal mucosa requires overcoming complex physiological barriers. The aim of this study is to modify PEGylated lipids to enhance the mucosal immune efficacy of the vaccine. Methods: The PEGylated lipid component of lipid nanoparticle (LNP) delivery vectors was modified with chitosan or mannose to generate novel LNPs that enhance vaccine adhesion or targeting on mucosal surfaces. The impact of the mRNA encoding the receptor-binding domain of Omicron BA.4/BA.5 on the immune response was examined. Results: Compared to the unmodified LNP group, the IgG and IgA titers in the chitosan or mannose-modified LNP groups showed an increasing trend. The chitosan-modified group showed better effects. Notably, the PEGylated lipid with 1.5 mol% of chitosan modification produced high levels of IgG1 and IgG2a antibodies, promoting Th1/Th2 responses while also generating high levels of IgA, which can induce stronger cellular immunity, humoral immunity, and mucosal immunity. Conclusions: The 1.5 mol% of chitosan-modified LNPs (mRNA-LNP-1.5CS) can serve as a safe and effective carrier for intranasal mRNA vaccines, offering a promising strategy for combating the Omicron variant.https://www.mdpi.com/1999-4923/16/11/1423chitosan-modified PEGylated lipidsmannose-modified PEGylated lipidslipid nanoparticlesmucosal immunitymRNA vaccine |
| spellingShingle | Meng Li Jing Yi Yicheng Lu Ting Liu Haonan Xing Xiwei Wang Hui Zhang Nan Liu Zengming Wang Aiping Zheng Modified PEG-Lipids Enhance the Nasal Mucosal Immune Capacity of Lipid Nanoparticle mRNA Vaccines Pharmaceutics chitosan-modified PEGylated lipids mannose-modified PEGylated lipids lipid nanoparticles mucosal immunity mRNA vaccine |
| title | Modified PEG-Lipids Enhance the Nasal Mucosal Immune Capacity of Lipid Nanoparticle mRNA Vaccines |
| title_full | Modified PEG-Lipids Enhance the Nasal Mucosal Immune Capacity of Lipid Nanoparticle mRNA Vaccines |
| title_fullStr | Modified PEG-Lipids Enhance the Nasal Mucosal Immune Capacity of Lipid Nanoparticle mRNA Vaccines |
| title_full_unstemmed | Modified PEG-Lipids Enhance the Nasal Mucosal Immune Capacity of Lipid Nanoparticle mRNA Vaccines |
| title_short | Modified PEG-Lipids Enhance the Nasal Mucosal Immune Capacity of Lipid Nanoparticle mRNA Vaccines |
| title_sort | modified peg lipids enhance the nasal mucosal immune capacity of lipid nanoparticle mrna vaccines |
| topic | chitosan-modified PEGylated lipids mannose-modified PEGylated lipids lipid nanoparticles mucosal immunity mRNA vaccine |
| url | https://www.mdpi.com/1999-4923/16/11/1423 |
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