Polyethylene glycol (PEG)-associated immune responses triggered by clinically relevant lipid nanoparticles in rats

Abstract With the large-scale vaccination of lipid nanoparticles (LNP)-based COVID-19 mRNA vaccines, elucidating the potential polyethylene glycol (PEG)-associated immune responses triggered by clinically relevant LNP has become imminent. However, inconsistent findings were observed across very limi...
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Autor*in:	Haiyang Wang [verfasserIn] Yisha Wang [verfasserIn] Changzheng Yuan [verfasserIn] Xiao Xu [verfasserIn] Wenbin Zhou [verfasserIn] Yuhui Huang [verfasserIn] Huan Lu [verfasserIn] Yue Zheng [verfasserIn] Gan Luo [verfasserIn] Jia Shang [verfasserIn] Meihua Sui [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Übergeordnetes Werk:	In: npj Vaccines - Nature Portfolio, 2017, 8(2023), 1, Seite 13
Übergeordnetes Werk:	volume:8 ; year:2023 ; number:1 ; pages:13

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1038/s41541-023-00766-z

Katalog-ID:	DOAJ095343547

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allfieldsSound	10.1038/s41541-023-00766-z doi (DE-627)DOAJ095343547 (DE-599)DOAJ478785326e8a4d74843672f7f1c2c26c DE-627 ger DE-627 rakwb eng RC581-607 RC254-282 Haiyang Wang verfasserin aut Polyethylene glycol (PEG)-associated immune responses triggered by clinically relevant lipid nanoparticles in rats 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract With the large-scale vaccination of lipid nanoparticles (LNP)-based COVID-19 mRNA vaccines, elucidating the potential polyethylene glycol (PEG)-associated immune responses triggered by clinically relevant LNP has become imminent. However, inconsistent findings were observed across very limited population-based studies. Herein we initiated a study using LNP carrier of Comirnaty® as a representative, and simulated real-world clinical practice covering a series of time points and various doses correlated with approved LNP-delivered drugs in a rat model. We demonstrated the time- and dose-dependency of LNP-induced anti-PEG antibodies in rats. As a thymus-independent antigen, LNP unexpectedly induced isotype switch and immune memory, leading to rapid enhancement and longer lasting time of anti-PEG IgM and IgG upon re-injection in rats. Importantly, initial LNP injection accelerated the blood clearance of subsequent dosing in rats. These findings refine our understandings on LNP and possibly other PEG derivatives, and may promote optimization of related premarket guidelines and clinical protocols. Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Yisha Wang verfasserin aut Changzheng Yuan verfasserin aut Xiao Xu verfasserin aut Wenbin Zhou verfasserin aut Yuhui Huang verfasserin aut Huan Lu verfasserin aut Yue Zheng verfasserin aut Gan Luo verfasserin aut Jia Shang verfasserin aut Meihua Sui verfasserin aut In npj Vaccines Nature Portfolio, 2017 8(2023), 1, Seite 13 (DE-627)87811839X (DE-600)2882262-6 20590105 nnns volume:8 year:2023 number:1 pages:13 https://doi.org/10.1038/s41541-023-00766-z kostenfrei https://doaj.org/article/478785326e8a4d74843672f7f1c2c26c kostenfrei https://doi.org/10.1038/s41541-023-00766-z kostenfrei https://doaj.org/toc/2059-0105 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2023 1 13
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source	In npj Vaccines 8(2023), 1, Seite 13 volume:8 year:2023 number:1 pages:13
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authorswithroles_txt_mv	Haiyang Wang @@aut@@ Yisha Wang @@aut@@ Changzheng Yuan @@aut@@ Xiao Xu @@aut@@ Wenbin Zhou @@aut@@ Yuhui Huang @@aut@@ Huan Lu @@aut@@ Yue Zheng @@aut@@ Gan Luo @@aut@@ Jia Shang @@aut@@ Meihua Sui @@aut@@
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callnumber-first	R - Medicine
author	Haiyang Wang
spellingShingle	Haiyang Wang misc RC581-607 misc RC254-282 misc Immunologic diseases. Allergy misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens Polyethylene glycol (PEG)-associated immune responses triggered by clinically relevant lipid nanoparticles in rats
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topic_title	RC581-607 RC254-282 Polyethylene glycol (PEG)-associated immune responses triggered by clinically relevant lipid nanoparticles in rats
topic	misc RC581-607 misc RC254-282 misc Immunologic diseases. Allergy misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_unstemmed	misc RC581-607 misc RC254-282 misc Immunologic diseases. Allergy misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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title	Polyethylene glycol (PEG)-associated immune responses triggered by clinically relevant lipid nanoparticles in rats
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title_full	Polyethylene glycol (PEG)-associated immune responses triggered by clinically relevant lipid nanoparticles in rats
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title_sort	polyethylene glycol (peg)-associated immune responses triggered by clinically relevant lipid nanoparticles in rats
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title_auth	Polyethylene glycol (PEG)-associated immune responses triggered by clinically relevant lipid nanoparticles in rats
abstract	Abstract With the large-scale vaccination of lipid nanoparticles (LNP)-based COVID-19 mRNA vaccines, elucidating the potential polyethylene glycol (PEG)-associated immune responses triggered by clinically relevant LNP has become imminent. However, inconsistent findings were observed across very limited population-based studies. Herein we initiated a study using LNP carrier of Comirnaty® as a representative, and simulated real-world clinical practice covering a series of time points and various doses correlated with approved LNP-delivered drugs in a rat model. We demonstrated the time- and dose-dependency of LNP-induced anti-PEG antibodies in rats. As a thymus-independent antigen, LNP unexpectedly induced isotype switch and immune memory, leading to rapid enhancement and longer lasting time of anti-PEG IgM and IgG upon re-injection in rats. Importantly, initial LNP injection accelerated the blood clearance of subsequent dosing in rats. These findings refine our understandings on LNP and possibly other PEG derivatives, and may promote optimization of related premarket guidelines and clinical protocols.
abstractGer	Abstract With the large-scale vaccination of lipid nanoparticles (LNP)-based COVID-19 mRNA vaccines, elucidating the potential polyethylene glycol (PEG)-associated immune responses triggered by clinically relevant LNP has become imminent. However, inconsistent findings were observed across very limited population-based studies. Herein we initiated a study using LNP carrier of Comirnaty® as a representative, and simulated real-world clinical practice covering a series of time points and various doses correlated with approved LNP-delivered drugs in a rat model. We demonstrated the time- and dose-dependency of LNP-induced anti-PEG antibodies in rats. As a thymus-independent antigen, LNP unexpectedly induced isotype switch and immune memory, leading to rapid enhancement and longer lasting time of anti-PEG IgM and IgG upon re-injection in rats. Importantly, initial LNP injection accelerated the blood clearance of subsequent dosing in rats. These findings refine our understandings on LNP and possibly other PEG derivatives, and may promote optimization of related premarket guidelines and clinical protocols.
abstract_unstemmed	Abstract With the large-scale vaccination of lipid nanoparticles (LNP)-based COVID-19 mRNA vaccines, elucidating the potential polyethylene glycol (PEG)-associated immune responses triggered by clinically relevant LNP has become imminent. However, inconsistent findings were observed across very limited population-based studies. Herein we initiated a study using LNP carrier of Comirnaty® as a representative, and simulated real-world clinical practice covering a series of time points and various doses correlated with approved LNP-delivered drugs in a rat model. We demonstrated the time- and dose-dependency of LNP-induced anti-PEG antibodies in rats. As a thymus-independent antigen, LNP unexpectedly induced isotype switch and immune memory, leading to rapid enhancement and longer lasting time of anti-PEG IgM and IgG upon re-injection in rats. Importantly, initial LNP injection accelerated the blood clearance of subsequent dosing in rats. These findings refine our understandings on LNP and possibly other PEG derivatives, and may promote optimization of related premarket guidelines and clinical protocols.
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title_short	Polyethylene glycol (PEG)-associated immune responses triggered by clinically relevant lipid nanoparticles in rats
url	https://doi.org/10.1038/s41541-023-00766-z https://doaj.org/article/478785326e8a4d74843672f7f1c2c26c https://doaj.org/toc/2059-0105
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author2	Yisha Wang Changzheng Yuan Xiao Xu Wenbin Zhou Yuhui Huang Huan Lu Yue Zheng Gan Luo Jia Shang Meihua Sui
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Polyethylene glycol (PEG)-associated immune responses triggered by clinically relevant lipid nanoparticles in rats

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