Impact of anti-PEG antibodies induced by SARS-CoV-2 mRNA vaccines

Abstract

The successful mRNA vaccines against COVID-19 contain polyethylene glycol (PEG) to stabilize the lipid nanoparticles. Recent data show that PEG-specific antibodies can be induced or boosted by mRNA vaccination. Further research is needed to study the potential links between PEG-specific antibodies, vaccine reactogenicity and enhanced clearance of other PEG-containing medicines.

Investigating Generation of Antibodies against the Lipid Nanoparticle Vector Following COVID-19 Vaccination with an mRNA Vaccine

“…51,52 It should be mentioned that, beyond allergic reactions, anti-LNP antibodies could also lead to fast clearance 22 or disintegration 23,53 of the LNPs, hence changing their biodistribution and ultimately rendering them non-efficacious. 34,49,54 The plasma content of the antibodies was studied using a novel microscopy-based assay, in which the antigen studied is the entire LNP as a complete entity. The benefit of this setup is that the ability of antibodies to bind to exact LNP surface is reflected, taking into account important parameters such as particle size (i.e., surface curvature), zeta potential, membrane fluidity, PEG density, etc.…”

“…We here studied the induction of antibodies with the ability to recognize LNPs, following exposure of human donors to mRNA vaccines. The generation of such antibodies are first and foremost relevant due to the booster doses of COVID-19 vaccines being administered to the population, and the potential use of PEGylated cytokines in the treatment of SARS-CoV-2 . Anti-LNP antibodies are, however, also of particular importance due to the high recent interest in LNPs and the many applications for which they may be used in the near future, including vaccines against common infectious diseases (such as seasonal influenza), protein replacement therapies, and cancer therapeutics. , It should be mentioned that, beyond allergic reactions, anti-LNP antibodies could also lead to fast clearance or disintegration , of the LNPs, hence changing their biodistribution and ultimately rendering them non-efficacious. ,, …”

The Usefulness of Nanotechnology in Improving the Prognosis of Lung Cancer

“…Polyethylene glycol (HO–(CH 2 CH 2 O) n–H) is soluble in both water and non-polar organic solvents and may be conjugated with various nanoparticles. PEGylated liposomes show improved circulation time and better tumor accumulation [ 13 , 14 ]; however, the presence of PEG-specific antibodies may limit the usefulness of such an add-on as anaphylaxis or complement-mediated destruction of the liposome may occur [ 15 , 16 , 17 ].…”

Visible Light Conjugation with Triazolinediones as a Route to Degradable Poly(ethylene glycol)–Lipids for mRNA Lipid Nanoparticle Formulation

“…PEG is a hydrophilic polymer that is used in many clinically‐approved drug formulations and is known to prolong blood circulation time and reduce opsonization of nanomedicines [9] . Despite the therapeutic benefits, administration of PEGylated proteins [10, 11] and PEGylated nanoparticles [12–15] can generate anti‐PEG antibodies in the host which is also reported in case of Covid‐19 vaccines [16] . Anti‐PEG antibodies result in accelerated blood clearance of the drug and, thereby, reduce therapeutic efficacy.…”

“…[9] Despite the therapeutic benefits, administration of PEGylated proteins [10,11] and PEGylated nanoparticles [12][13][14][15] can generate anti-PEG antibodies in the host which is also reported in case of Covid-19 vaccines. [16] Anti-PEG antibodies result in accelerated blood clearance of the drug and, thereby, reduce therapeutic efficacy. Long term accumulation of PEG in the body has also fostered the quest for PEG alternatives [17,18] and strategies that reduce the exposure to PEG.…”