Anti-PEG Antibodies From mRNA COVID-19 Vaccines Affect In Vitro Measurements of Pegylated Drug Levels.

The recent adoption of mRNA-based technology for vaccine development has led to widespread exposure to new vaccine components, such as polyethylene glycol (PEG), against which antibodies may be made. This study assesses the presence of anti-PEG antibodies in human serum following SARS-CoV-2 vaccination, and if these antibodies could interfere with drug level assessment of PEG containing drugs. Elevated anti-PEG antibody titers with prolonged prevalence were detected in individuals who received the mRNA-1273 vaccine as compared to control samples. Anti-PEG antibody levels were approximately 10-fold higher post-vaccination compared to pre-vaccination in approximately 33% of assessed mRNA-1273 vaccine recipients. Elevated anti-PEG antibody levels persisted for over 6 months. Serum from those who received the BNT162b2 or Ad26.COV2.S vaccines had anti-PEG antibody levels similar to control samples. Serum from individuals with elevated anti-PEG antibodies, regardless of study group, typically showed decreased detection of the pegylated drug, pegfilgrastim. This study demonstrates that anti-PEG antibodies have the potential to interfere with bioanalytical assays used for pharmacokinetic drug measurement during the development of pegylated pharmaceutical products, as well as during the establishment of comparability to pegylated reference products during development of biosimilar drug products.