Polyethylene glycol-specific antibody (Anti-PEG antibody) (Anti-PEG Ab)

Polyethylene glycol (PEG)-specific antibodies (Anti-PEG Abs) are immunoglobulins that recognize the repeating ethylene oxide subunits of PEG polymers, which are commonly used to coat lipid nanoparticles (LNPs) to improve stability and circulation time (Kozma et al., 2020, ACS Nano). These antibodies can be pre-existing in the general population due to exposure to PEG in cosmetics and processed foods, or they can be induced following the administration of PEGylated therapeutics (Zhang et al., 2016, Analytical Chemistry). When anti-PEG antibodies bind to the PEGylated lipids on the surface of an LNP, they can trigger the classical complement pathway and opsonize the particle for rapid uptake by the mononuclear phagocyte system, primarily in the liver and spleen (Dams et al., 2000, Journal of Pharmacology and Experimental Therapeutics). This process, known as the accelerated blood clearance (ABC) phenomenon, significantly reduces the half-life and therapeutic efficacy of the drug (Abu Lila et al., 2013, Journal of Controlled Release). Additionally, the formation of these immune complexes can lead to acute hypersensitivity reactions, such as complement-activation-related pseudoallergy (CARPA), which may manifest as anaphylaxis (Szebeni, 2005, Molecular Immunology). Consequently, anti-PEG antibodies represent a significant challenge for the development of mRNA vaccines and other LNP-based genetic medicines.

Other names

Anti-PEG antibodyPEG-specific antibodyAnti-polyethylene glycol antibodyAnti-PEG IgMAnti-PEG IgG

Anti-PEG antibodies bind to the PEG moiety on the surface of lipid nanoparticles (LNPs), triggering the classical complement pathway and opsonization, which leads to rapid uptake by the mononuclear phagocyte system (MPS).