Regulating Immune Responses Induced by PEGylated Messenger RNA–Lipid Nanoparticle Vaccine
Messenger RNA (mRNA)-based therapeutics have shown remarkable progress in the treatment and prevention of diseases. Lipid nanoparticles (LNPs) have shown great successes in delivering mRNAs. After an mRNA-LNP vaccine enters a cell via an endosome, mRNA is translated into an antigen, which can activa...
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| Format: | Article |
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MDPI AG
2024-12-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/13/1/14 |
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| author | Hyein Jo Jaewhoon Jeoung Wonho Kim Dooil Jeoung |
| author_facet | Hyein Jo Jaewhoon Jeoung Wonho Kim Dooil Jeoung |
| author_sort | Hyein Jo |
| collection | DOAJ |
| description | Messenger RNA (mRNA)-based therapeutics have shown remarkable progress in the treatment and prevention of diseases. Lipid nanoparticles (LNPs) have shown great successes in delivering mRNAs. After an mRNA-LNP vaccine enters a cell via an endosome, mRNA is translated into an antigen, which can activate adaptive immunity. mRNAs can bind to various pattern recognition receptors (PRRs), including toll-like receptors (TLRs), and increase the production of inflammatory cytokines. This review summarizes mechanisms of innate immunity induced by mRNAs. Polyethylene glycol (PEG) has been employed as a component of the mRNA-LNP vaccine. PEGylated nanoparticles display enhanced stability by preventing aggregation of particles. However, PEGylation can cause adverse reactions, including blood clearance (ABC) of nanoparticles via complement activation and anaphylaxis. Mechanisms of PEG-induced ABC phenomenon and anaphylaxis are presented and discussed. There have been studies aimed at reducing immune responses associated with PEG to make safe and effective vaccines. Effects of modifying or replacing PEG in reducing immune responses associated with PEGylated nanoparticles are also discussed. Modifying mRNA can induce immune tolerance, which can prevent hypersensitivity reactions induced by PEGylated mRNA-LNP vaccines. Current progress of immune tolerance induction in association with mRNA-LNP is also summarized. This review might be helpful for developing safe and effective PEGylated mRNA-LNP vaccines. |
| format | Article |
| id | doaj-art-7cc1481cb2f14cf5b7b399115cda275b |
| institution | Kabale University |
| issn | 2076-393X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj-art-7cc1481cb2f14cf5b7b399115cda275b2025-01-24T13:51:40ZengMDPI AGVaccines2076-393X2024-12-011311410.3390/vaccines13010014Regulating Immune Responses Induced by PEGylated Messenger RNA–Lipid Nanoparticle VaccineHyein Jo0Jaewhoon Jeoung1Wonho Kim2Dooil Jeoung3Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon 24341, Republic of KoreaDepartment of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon 24341, Republic of KoreaDepartment of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon 24341, Republic of KoreaDepartment of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon 24341, Republic of KoreaMessenger RNA (mRNA)-based therapeutics have shown remarkable progress in the treatment and prevention of diseases. Lipid nanoparticles (LNPs) have shown great successes in delivering mRNAs. After an mRNA-LNP vaccine enters a cell via an endosome, mRNA is translated into an antigen, which can activate adaptive immunity. mRNAs can bind to various pattern recognition receptors (PRRs), including toll-like receptors (TLRs), and increase the production of inflammatory cytokines. This review summarizes mechanisms of innate immunity induced by mRNAs. Polyethylene glycol (PEG) has been employed as a component of the mRNA-LNP vaccine. PEGylated nanoparticles display enhanced stability by preventing aggregation of particles. However, PEGylation can cause adverse reactions, including blood clearance (ABC) of nanoparticles via complement activation and anaphylaxis. Mechanisms of PEG-induced ABC phenomenon and anaphylaxis are presented and discussed. There have been studies aimed at reducing immune responses associated with PEG to make safe and effective vaccines. Effects of modifying or replacing PEG in reducing immune responses associated with PEGylated nanoparticles are also discussed. Modifying mRNA can induce immune tolerance, which can prevent hypersensitivity reactions induced by PEGylated mRNA-LNP vaccines. Current progress of immune tolerance induction in association with mRNA-LNP is also summarized. This review might be helpful for developing safe and effective PEGylated mRNA-LNP vaccines.https://www.mdpi.com/2076-393X/13/1/14ABC phenomenonallergiescomplementimmune toleranceinnate immunitymRNA-LNPs |
| spellingShingle | Hyein Jo Jaewhoon Jeoung Wonho Kim Dooil Jeoung Regulating Immune Responses Induced by PEGylated Messenger RNA–Lipid Nanoparticle Vaccine Vaccines ABC phenomenon allergies complement immune tolerance innate immunity mRNA-LNPs |
| title | Regulating Immune Responses Induced by PEGylated Messenger RNA–Lipid Nanoparticle Vaccine |
| title_full | Regulating Immune Responses Induced by PEGylated Messenger RNA–Lipid Nanoparticle Vaccine |
| title_fullStr | Regulating Immune Responses Induced by PEGylated Messenger RNA–Lipid Nanoparticle Vaccine |
| title_full_unstemmed | Regulating Immune Responses Induced by PEGylated Messenger RNA–Lipid Nanoparticle Vaccine |
| title_short | Regulating Immune Responses Induced by PEGylated Messenger RNA–Lipid Nanoparticle Vaccine |
| title_sort | regulating immune responses induced by pegylated messenger rna lipid nanoparticle vaccine |
| topic | ABC phenomenon allergies complement immune tolerance innate immunity mRNA-LNPs |
| url | https://www.mdpi.com/2076-393X/13/1/14 |
| work_keys_str_mv | AT hyeinjo regulatingimmuneresponsesinducedbypegylatedmessengerrnalipidnanoparticlevaccine AT jaewhoonjeoung regulatingimmuneresponsesinducedbypegylatedmessengerrnalipidnanoparticlevaccine AT wonhokim regulatingimmuneresponsesinducedbypegylatedmessengerrnalipidnanoparticlevaccine AT dooiljeoung regulatingimmuneresponsesinducedbypegylatedmessengerrnalipidnanoparticlevaccine |