Polyethylene Glycol Immunogenicity: Theoretical, Clinical, and Practical Aspects of Anti-Polyethylene Glycol Antibodies

• Published in: ACS nano Vol. 15; no. 9; pp. 14022 - 14048
• Main Authors: Chen, Bing-Mae, Cheng, Tian-Lu, Roffler, Steve R
• Format: Journal Article
• Language: English
• Published: American Chemical Society 28.09.2021
• Subjects: polyethylene glycol; thymus-independent type-2 (TI-2) antigen; humoral immunity; anti-PEG antibodies; pegylation; accelerated blood clearance; SARS-CoV-2 RNA vaccines; pre-existing antibodies; lipo­somes; immunogenicity
• ISSN: 1936-0851; 1936-086X; 1936-086X
• DOI: 10.1021/acsnano.1c05922

Polyethylene glycol (PEG) is a flexible, hydrophilic simple polymer that is physically attached to peptides, proteins, nucleic acids, lipo­somes, and nanoparticles to reduce renal clearance, block antibody and protein binding sites, and enhance the half-life and efficacy of therapeutic molecules. Some naïve individuals have pre-existing antibodies that can bind to PEG, and some PEG-modified compounds induce additional antibodies against PEG, which can adversely impact drug efficacy and safety. Here we provide a framework to better understand PEG immunogenicity and how antibodies against PEG affect pegylated drug and nanoparticles. Analysis of published studies reveals rules for predicting accelerated blood clearance of pegylated medicine and therapeutic lipo­somes. Experimental studies of anti-PEG antibody binding to different forms, sizes, and immobilization states of PEG are also provided. The widespread use of SARS-CoV-2 RNA vaccines that incorporate PEG in lipid nanoparticles make understanding possible effects of anti-PEG antibodies on pegylated medicines even more critical.