Ju Yi, Lee Wen Shi, Pilkington Emily H, Kelly Hannah G, Li Shiyao, Selva Kevin J, Wragg Kathleen M, Subbarao Kanta, Nguyen Thi H O, Rowntree Louise C, Allen Lilith F, Bond Katherine, Williamson Deborah A, Truong Nghia P, Plebanski Magdalena, Kedzierska Katherine, Mahanty Siddhartha, Chung Amy W, Caruso Frank, Wheatley Adam K, Juno Jennifer A, Kent Stephen J
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia.
School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia.
ACS Nano. 2022 Aug 23;16(8):11769-11780. doi: 10.1021/acsnano.2c04543. Epub 2022 Jun 27.
Humans commonly have low level antibodies to poly(ethylene) glycol (PEG) due to environmental exposure. Lipid nanoparticle (LNP) mRNA vaccines for SARS-CoV-2 contain small amounts of PEG, but it is not known whether PEG antibodies are enhanced by vaccination and what their impact is on particle-immune cell interactions in human blood. We studied plasma from 130 adults receiving either the BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) mRNA vaccines or no SARS-CoV-2 vaccine for PEG-specific antibodies. Anti-PEG IgG was commonly detected prior to vaccination and was significantly boosted a mean of 13.1-fold (range 1.0-70.9) following mRNA-1273 vaccination and a mean of 1.78-fold (range 0.68-16.6) following BNT162b2 vaccination. Anti-PEG IgM increased 68.5-fold (range 0.9-377.1) and 2.64-fold (0.76-12.84) following mRNA-1273 and BNT162b2 vaccination, respectively. The rise in PEG-specific antibodies following mRNA-1273 vaccination was associated with a significant increase in the association of clinically relevant PEGylated LNPs with blood phagocytes ex vivo. PEG antibodies did not impact the SARS-CoV-2 specific neutralizing antibody response to vaccination. However, the elevated levels of vaccine-induced anti-PEG antibodies correlated with increased systemic reactogenicity following two doses of vaccination. We conclude that PEG-specific antibodies can be boosted by LNP mRNA vaccination and that the rise in PEG-specific antibodies is associated with systemic reactogenicity and an increase of PEG particle-leukocyte association in human blood. The longer-term clinical impact of the increase in PEG-specific antibodies induced by lipid nanoparticle mRNA vaccines should be monitored. It may be useful to identify suitable alternatives to PEG for developing next-generation LNP vaccines to overcome PEG immunogenicity in the future.
由于环境暴露，人类通常对聚乙二醇（PEG）有低水平抗体。用于严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的脂质纳米颗粒（LNP）信使核糖核酸（mRNA）疫苗含有少量PEG，但尚不清楚接种疫苗是否会增强PEG抗体，以及它们对人血液中颗粒-免疫细胞相互作用有何影响。我们研究了130名接受BNT162b2（辉瑞-生物科技公司）或mRNA-1273（莫德纳公司）mRNA疫苗或未接种SARS-CoV-2疫苗的成年人血浆中的PEG特异性抗体。接种疫苗前通常可检测到抗PEG IgG，mRNA-1273疫苗接种后平均升高13.1倍（范围1.0-70.9），BNT162b2疫苗接种后平均升高1.78倍（范围0.68-16.6）。mRNA-1273和BNT162b2疫苗接种后，抗PEG IgM分别增加68.5倍（范围0.9-377.1）和2.64倍（0.76-12.84）。mRNA-1273疫苗接种后PEG特异性抗体的升高与临床相关聚乙二醇化LNP与体外血液吞噬细胞的结合显著增加有关。PEG抗体不影响对疫苗接种的SARS-CoV-2特异性中和抗体反应。然而，疫苗诱导的抗PEG抗体水平升高与两剂疫苗接种后全身反应原性增加相关。我们得出结论，LNP mRNA疫苗可增强PEG特异性抗体，PEG特异性抗体的升高与全身反应原性以及人血液中PEG颗粒-白细胞结合增加有关。应监测脂质纳米颗粒mRNA疫苗诱导的PEG特异性抗体增加的长期临床影响。识别PEG的合适替代品以开发下一代LNP疫苗，可能有助于在未来克服PEG的免疫原性。
