Anti-PEG: Monoclonal Antibody Against Polyethylene Glycol

The Rise of Anti-PEG Antibodies

Anti-peg chemistry

Looking to choose PEG reagents and PEGylation chemistry to deliver better-performing pharmaceutical products facing the rise of anti-polyethylene glycol (anti-PEG) antibodies in the human circulatory system?

This blog talks about anti-PEG antibodies, how they could affect the performance of medicines, and how Creative PEGWorks can help your projects.   

Detect and Measure PEG, Pegylated Proteins

Humans are exposed to poly(ethylene) glycol (PEG) through consumer products, cosmetic products, and medicines. A proportion of adults have low levels of circulating anti-polyethylene glycol antibody (anti-PEG antibody) in their bloodstream. An antibody also known as an immunoglobulin is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as chemical molecules. The antibody recognizes a unique portion of a molecule; the molecule is called an antigen and the portion of the molecule that is specifically recognized by the antibody is called an epitope. Each tip of the “Y” of an antibody is specific for one particular epitope on an antigen, allowing these two structures to bind together with precision. For anti-PEG antibodies, PEG is the antigen. The most common antibody is Y-shaped immunoglobulin G, IgG.

Why Utilize PEG

PEG is a water-soluble, nontoxic, biocompatible polymer that has been approved by the Food and Drug Administration (FDA) for human intravenous, oral and dermal applications. PEG is often used as an inactive ingredient in the pharmaceutical industry as a solvent, plasticizer, surfactant, ointments, and suppository base, and tablet and capsule lubricant. PEG has low toxicity with systemic absorption of less than 0.5%. For example, PEG 3350 (PEG with a molecular weight of 3350) is a laxative to treat constipation and used for bowel preparation before colonoscopies and other procedures. Its brand names include: Bi-peglyte, Clearlax, Colyte, Gavilax, Gavilyte-C, Gavilyte-G, Gavilyte-H and Bisacodyl, Gavilyte-N, Gentlelax, Gialax, Glycolax, Golytely, Healthylax, Miralax, Moviprep, Nulytely, Peglyte, Pegylax, Plenvu, Purelax.

Attachment of PEG chains to proteins can reduce their immunogenicity, minimize proteolytic cleavage and increase their blood circulation half-life. PEG has also been attached to small molecules, liposomes, and lipid nanoparticles for more selective drug delivery. The process of both covalent and non-covalent attachment or amalgamation of polyethylene glycol polymer chains to molecules and macrostructures, such as a drug, therapeutic protein, or vesicle, is called PEGylation. The product of the PEGylation is then described as PEGylated. PEGylation is routinely achieved by the incubation of a reactive derivative of PEG with the target molecule. The covalent attachment of PEG to a drug or therapeutic protein can “mask” the agent from the host’s immune system (reducing immunogenicity and antigenicity), and increase its hydrodynamic size (size in solution), which prolongs its circulatory time by reducing renal clearance. PEGylation can also provide water solubility to hydrophobic drugs and proteins. A full list of commercially available PEGylated pharmaceuticals is included at the end of this blog.

Where Do Anti-PEG Antibodies Come In?

However, incorporation of PEG into the formulation of systemically administered drugs to improve pharmacokinetics can result in anti-PEG antibodies that ultimately limit the bioavailability of the drug and can potentially cause side effects. The most recent clinical examples of using PEG technology in FDA approved medicines are COVID-19 vaccine. Lipid nanoparticle (LNP) mRNA vaccines for SARS-CoV-2 (COVID-19) contain small amounts of PEG−lipid conjugates to stabilize the LNPs. An estimated 50 and 117 μg of PEG−lipid conjugates are present per dose for the BNT162b2 (The Pfizer-BioNTech COVID-19 Vaccine) and mRNA-1273 (The Moderna COVID-19 Vaccine) vaccines, respectively. Over ten billion doses of SARS-CoV-2 vaccines have now been given worldwide. Studies have found that anti-PEG IgG was commonly detected prior to vaccination and was significantly boosted by a mean of 13.1-fold following mRNA-1273 vaccination and a mean of 1.78-fold following BNT162b2 vaccination (1). Although PEG antibodies were not found to impact the SARS-CoV-2 specific neutralizing antibody response to vaccination, the elevated levels of vaccine-induced anti-PEG antibodies could cause potential issues and shall be continuously monitored.

Quality Matters with PEG or Anti-Polyethylene Glycol Products

With PEG being used in increasingly more pharmaceutical products, researchers must be very careful in selecting PEG reagents in their research to conduct PEGylation of proteins, nanoparticles, nucleic acids, small molecules, in order to achieve the best pharmaceutical performance. 

PEG is a long polymer that could have multiple epitopes to illicit host immune response generating anti-PEG antibodies. 

Below are all critical questions researchers need to consider in selecting PEG reagents for their research. 

  • How the PEG is conjugated to the target pharmaceutical agent? 
  • How long is the PEG? 
  • How many PEG polymers for each pharmaceutical molecule or nanoparticle? 
  • What is the density of the PEG coating on nanoparticle surface? 

Contact Creative PEGWorks for High-Quality PEG Products

Creative PEGWorks have the largest collection of PEG reagents, has served the PEGylation industry and research community for more than 15 years, and has decades of hands-on experience in PEGylation ready to help your projects. Please visit us online to view and purchase our variety of PEG products and contact us for technical support.


Commercially available PEGylated pharmaceuticals on the market are listed in reverse chronology by FDA approval year:

1)       A PEGylated lipid is used as an excipient in both the Moderna vaccine and the Pfizer–BioNTech COVID-19 vaccine.

2)       Pegvaliase (Biomarin) – PEGylated recombinant phenylalanine ammonia-lyase, approved by the FDA for the US in May 2018.

3)       Adynovate – PEGylated Antihemophilic Factor VIII, approved in 2015.

4)       Irinotecan liposome (Onivyde) – PEGylated liposomal irinotecan hydrochloride trihydrate, approved in 2015

5)       Plegridy – PEGylated Interferon Beta-1a, approved in 2014

6)       Naloxegol (Movantik) – PEGylated naloxol, approved in 2014

7)       Peginesatide (Omontys) – PEGylated synthetic peptide, approved in 2012

8)       Pegloticase (Krystexxa) – PEGylated uricase, approved in 2010

9)       Certolizumab pegol (Cimzia) – PEGylated monoclonal antibody, approved in 2008

10)   Methoxy polyethylene glycol-epoetin beta (Mircera) – PEGylated form of erythropoietin, approved in 2007

11)   Pegaptanib (Macugen) – PEGylated anti-vascular endothelial growth factor (VEGF) aptamer, a single strand of nucleic acid, approved in 2004

12)   Pegfilgrastim (Neulasta) – PEGylated recombinant methionyl human granulocyte colony-stimulating factor, approved in 2002

13)   Pegvisomant (Somavert) – PEG-human growth hormone mutein receptor antagonist, approved in 2002

14)   Peginterferon alfa-2a (Pegasys) – PEGylated interferon alpha, approved in 2002

15)   Peginterferon alfa-2b (PegIntron) – PEGylated interferon alpha, approved in 2000

16)   Doxorubicin HCl liposome (Doxil/Caelyx) – PEGylated liposome containing doxorubicin, approved in 1995

17)   Pegaspargase (Oncaspar) – PEGylated L-asparaginase, approved in 1994

18)   Pegademase bovine (Adagen) – PEG-adenosine deaminase, approved in 1990

Reference: (1) Anti-PEG Antibodies Boosted in Humans by SARS-CoV-2 Lipid Nanoparticle mRNA Vaccine | ACS Nano