[P]olymer conjugation [PEG / synthetic polymer] has demonstrated… clinical utility in stabilizing lipid nanoparticles… [used to deliver mRNA for] both current mRNA-based vaccines for SARS-CoV-2 (COVID-19), BNT162b2/Comirnaty and mRNA-1273/Spikevax.
[T]heir widespread use has led to concerns from some that pre-existing anti-PEG antibodies may induce hypersensitivity reactions…
PEG’s remarkable hydrophilicity, flexibility, inertness, and relative biocompatibility have found the polymer numerous uses beyond modulating drug circulation or activity and today it can be found near ubiquitously in both consumer products such as detergents, cosmetics, and car wax, as well as in industrial applications including electroplating, historical artifact preservation, and molded product production.
Given PEG’s near exclusive utilization in polymer-drug conjugates, our rapidly increasing consumer use of the compound, and recent, prevalent, and systemic exposure to PEG in the form of mRNA vaccines and boosters for SARS-CoV-2 (currently >0.5 bn doses in the United States) several obvious questions arise with relevance to both public awareness and public health…
PEG was classified as a GRAS (Generally Recognized as Safe) food ingredient by the FDA in 1973…
[T]he presence of pre-existing anti- PEG antibodies has been reported to range from 4.5 to 43.1% in treatment-naïve donors…
Recent analysis of 79 historical (samples collected from the 1970s–1990s) and 377 contemporary human serum samples, indicate the presence of anti-PEG antibodies (IgG and IgM) in approximately 56 and 72% of samples respectively…
Hypersensitivity reactions, including anaphylaxis has been reported in association with many PEG-containing formulations including… PEG excipients (polysorbate 80)… liposomes encapsulating oligonucleotides or plasmid DNA…
Pre- existing PEG antibodies, in contrast, have been implicated in hypersensitivity reactions to PEGylated medicines…
Acute severe allergic reactions to pegnivacogin* were observed only in patients with pre-existing anti-PEG antibodies, and the level of anti-PEG IgG antibodies correlated with adverse event severity.
[A]nti-PEG antibodies induced by one PEGylated medicines can cross-react to other subsequently administered PEGylated medicines. The mechanism(s) by which anti-PEG antibodies induce hypersensitivity reactions is poorly understood…