Durable protective efficiency provide by mRNA vaccines require robust immune memory to antigens and weak immune memory to lipid nanoparticles
The Pegylated lipids in lipid nanoparticle (LNPs) vaccines have been found to cause acute hypersensitivity reactions in recipients, and generate anti-LNPs immunity after repeated administration, thereby reducing vaccine effectiveness. To overcome these challenges, we developed a new type of LNPs vac...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | Materials Today Bio |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006424000474 |
| _version_ | 1797258669697531904 |
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| author | Xueying Tang Jiashuo Zhang Dezhi Sui Zihan Xu Qiongfen Yang Tianyu Wang Xiaoya Li Xinrong Liu Yihui Deng Yanzhi Song |
| author_facet | Xueying Tang Jiashuo Zhang Dezhi Sui Zihan Xu Qiongfen Yang Tianyu Wang Xiaoya Li Xinrong Liu Yihui Deng Yanzhi Song |
| author_sort | Xueying Tang |
| collection | DOAJ |
| description | The Pegylated lipids in lipid nanoparticle (LNPs) vaccines have been found to cause acute hypersensitivity reactions in recipients, and generate anti-LNPs immunity after repeated administration, thereby reducing vaccine effectiveness. To overcome these challenges, we developed a new type of LNPs vaccine (SAPC-LNPs) which was co-modified with sialic acid (SA) - lipid derivative and cleavable PEG - lipid derivative. This kind of mRNA vaccine can target dendritic cells (DCs) and rapidly escape from early endosomes (EE) and lysosomes with a total endosomal escape rate up to 98 %. Additionally, the PEG component in SAPC-LNPs was designed to detach from the LNPs under the catalysis of carboxylesterase in vivo, which reduced the probability of PEG being attached to LNPs entering antigen-presenting cells. Compared with commercially formulated vaccines (1.5PD-LNPs), mice treated with SAPC-LNPs generated a more robust immune memory to tumor antigens and a weaker immune memory response to LNPs, and showed lower side effects and long-lasting protective efficiency. We also discovered that the anti-tumor immune memory formed by SAPC-LNPs mRNA vaccine was directly involved in the immune cycle to rattack tumor. This immune memory continued to strengthen with multiple cycles, supporting that the immune memory should be incorporated into the theory of tumor immune cycle. |
| first_indexed | 2024-03-08T00:23:01Z |
| format | Article |
| id | doaj.art-8f0b3acc1ca24533802b1fb76504328c |
| institution | Directory Open Access Journal |
| issn | 2590-0064 |
| language | English |
| last_indexed | 2024-04-24T22:57:13Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj.art-8f0b3acc1ca24533802b1fb76504328c2024-03-18T04:34:22ZengElsevierMaterials Today Bio2590-00642024-04-0125100988Durable protective efficiency provide by mRNA vaccines require robust immune memory to antigens and weak immune memory to lipid nanoparticlesXueying Tang0Jiashuo Zhang1Dezhi Sui2Zihan Xu3Qiongfen Yang4Tianyu Wang5Xiaoya Li6Xinrong Liu7Yihui Deng8Yanzhi Song9College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, ChinaCollege of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, ChinaCollege of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, ChinaCollege of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, ChinaCollege of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, ChinaCollege of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, ChinaCollege of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, ChinaCollege of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, ChinaCorresponding author.; College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, ChinaCorresponding author.; College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, ChinaThe Pegylated lipids in lipid nanoparticle (LNPs) vaccines have been found to cause acute hypersensitivity reactions in recipients, and generate anti-LNPs immunity after repeated administration, thereby reducing vaccine effectiveness. To overcome these challenges, we developed a new type of LNPs vaccine (SAPC-LNPs) which was co-modified with sialic acid (SA) - lipid derivative and cleavable PEG - lipid derivative. This kind of mRNA vaccine can target dendritic cells (DCs) and rapidly escape from early endosomes (EE) and lysosomes with a total endosomal escape rate up to 98 %. Additionally, the PEG component in SAPC-LNPs was designed to detach from the LNPs under the catalysis of carboxylesterase in vivo, which reduced the probability of PEG being attached to LNPs entering antigen-presenting cells. Compared with commercially formulated vaccines (1.5PD-LNPs), mice treated with SAPC-LNPs generated a more robust immune memory to tumor antigens and a weaker immune memory response to LNPs, and showed lower side effects and long-lasting protective efficiency. We also discovered that the anti-tumor immune memory formed by SAPC-LNPs mRNA vaccine was directly involved in the immune cycle to rattack tumor. This immune memory continued to strengthen with multiple cycles, supporting that the immune memory should be incorporated into the theory of tumor immune cycle.http://www.sciencedirect.com/science/article/pii/S2590006424000474mRNA cancer vaccineImmune memoryLipid nanoparticlesSialic acidTumor immune cycle |
| spellingShingle | Xueying Tang Jiashuo Zhang Dezhi Sui Zihan Xu Qiongfen Yang Tianyu Wang Xiaoya Li Xinrong Liu Yihui Deng Yanzhi Song Durable protective efficiency provide by mRNA vaccines require robust immune memory to antigens and weak immune memory to lipid nanoparticles Materials Today Bio mRNA cancer vaccine Immune memory Lipid nanoparticles Sialic acid Tumor immune cycle |
| title | Durable protective efficiency provide by mRNA vaccines require robust immune memory to antigens and weak immune memory to lipid nanoparticles |
| title_full | Durable protective efficiency provide by mRNA vaccines require robust immune memory to antigens and weak immune memory to lipid nanoparticles |
| title_fullStr | Durable protective efficiency provide by mRNA vaccines require robust immune memory to antigens and weak immune memory to lipid nanoparticles |
| title_full_unstemmed | Durable protective efficiency provide by mRNA vaccines require robust immune memory to antigens and weak immune memory to lipid nanoparticles |
| title_short | Durable protective efficiency provide by mRNA vaccines require robust immune memory to antigens and weak immune memory to lipid nanoparticles |
| title_sort | durable protective efficiency provide by mrna vaccines require robust immune memory to antigens and weak immune memory to lipid nanoparticles |
| topic | mRNA cancer vaccine Immune memory Lipid nanoparticles Sialic acid Tumor immune cycle |
| url | http://www.sciencedirect.com/science/article/pii/S2590006424000474 |
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