Effects of PEG antibodies on in vivo performance of LNP-mRNA vaccines.

Autor: Yang M; Department of Pharmacology, School of Basic Medical Sciences & Department of Pharmacy, Shanghai Pudong Hospital, Pudong Medical Center, Fudan University, Shanghai 200032, PR China., Zhang Z; Department of Pharmacology, School of Basic Medical Sciences & Department of Pharmacy, Shanghai Pudong Hospital, Pudong Medical Center, Fudan University, Shanghai 200032, PR China., Jin P; Department of Pharmacology, School of Basic Medical Sciences & Department of Pharmacy, Shanghai Pudong Hospital, Pudong Medical Center, Fudan University, Shanghai 200032, PR China; Department of Chronic Disease Management, Shanghai Pudong Hospital, Fudan University, Shanghai 201399, PR China., Jiang K; Department of Pharmacology, School of Basic Medical Sciences & Department of Pharmacy, Shanghai Pudong Hospital, Pudong Medical Center, Fudan University, Shanghai 200032, PR China; Department of Ophthalmology, Eye and ENT Hospital, Fudan University, Shanghai 200031, PR China., Xu Y; State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai, 200438 PR China., Pan F; School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, Shanghai 201203, PR China., Tian K; Department of Pharmacology, School of Basic Medical Sciences & Department of Pharmacy, Shanghai Pudong Hospital, Pudong Medical Center, Fudan University, Shanghai 200032, PR China., Yuan Z; Department of Pharmacology, School of Basic Medical Sciences & Department of Pharmacy, Shanghai Pudong Hospital, Pudong Medical Center, Fudan University, Shanghai 200032, PR China., Liu XE; DSciLab Co., Ltd, Shanghai 201210, PR China., Fu J; Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai 200032, PR China., Wang B; Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai 200032, PR China., Yan H; Department of Health Management, Pudong Hospital, Fudan University, Shanghai 201399, PR China., Zhan C; Department of Pharmacology, School of Basic Medical Sciences & Department of Pharmacy, Shanghai Pudong Hospital, Pudong Medical Center, Fudan University, Shanghai 200032, PR China; State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai, 200438 PR China; Shanghai Engineering Research Center for Synthetic Immunology, Fudan University, Shanghai 200032, PR China. Electronic address: cyzhan@fudan.edu.cn., Zhang Z; Department of Pharmacology, School of Basic Medical Sciences & Department of Pharmacy, Shanghai Pudong Hospital, Pudong Medical Center, Fudan University, Shanghai 200032, PR China. Electronic address: zhangzui@fudan.edu.cn.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2024 Jan 25; Vol. 650, pp. 123695. Date of Electronic Publication: 2023 Dec 09.
DOI: 10.1016/j.ijpharm.2023.123695
Abstrakt: Polyethylene glycol (PEG) plays important roles in stabilizing and lengthening circulation time of lipid nanoparticle (LNP) vaccines. Nowadays various levels of PEG antibodies have been detected in human blood, but the impact and mechanism of PEG antibodies on the in vivo performance of LNP vaccines has not been clarified thoroughly. By illustrating the distribution characteristics of PEG antibodies in human, the present study focused on the influence of PEG antibodies on the safety and efficacy of LNP-mRNA vaccine against COVID-19 in animal models. It was found that PEG antibodies led to shortened blood circulation duration, elevated accumulation and mRNA expression in liver and spleen, enhanced expression in macrophage and dendritic cells, while without affecting the production of anti-Spike protein antibodies of COVID-19 LNP vaccine. Noteworthily, PEG antibodies binding on the LNP vaccine increased probability of complement activation in animal as well as in human serum and led to lethal side effect in large dosage via intravenous injection of mice. Our data suggested that PEG antibodies in human was a risky factor of LNP-based vaccines for biosafety concerns but not efficacy.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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