PhD Scientific Days 2024

Theoretical and Translational Medicine I.

Characterizing Antibody Avidity Against Polyethylene Glycol Using the Traditional ELISA Method

Text of the abstract

Polyethylene glycol (PEG) and PEG-conjugated therapeutic agents have been widely used in medicine over the last two decades, sparking increased interest in immune responses against PEGylated carriers. Notably, the number of patients treated with PEGylated therapeutics has increased significantly in recent years, particularly with the use of PEG-conjugated lipid nanoparticle drug delivery systems in vaccines such as Comirnaty and Spikevax. Based on our previous results, anti-PEG antibody levels were significantly increased following these vaccines and we found that elevated anti-PEG antibody levels were associated with the severity of hypersensitivity reactions to vaccination. However, the interaction of anti-PEG antibodies with PEGylated product is influenced not only by concentration but also by antibody avidity, which affects immune complex formation, effector functions, and immune complex clearance.
Our study aimed to determine how treatment with PEGylated therapeutic agents impacts the average binding avidity of anti-PEG antibodies to PEGylated nanoparticles mimicking drug carriers.
We determined the average binding avidity of anti-PEG antibodies in plasma samples from Comirnaty and Spikevax vaccinated individuals, as well as COVID-19 unvaccinated volunteers, using the traditional ELISA method described by Friguet et al. Additionally, we employed an alternative approach suggested by Bobrovnik et al. for more accurate determination of average equilibrium constants of the anti-PEG antibodies.
Our results indicate that individuals who received Comirnaty and Spikevax vaccines have significantly higher anti-PEG antibody avidity compared to those who did not receive PEG-conjugated COVID-19 vaccination. Furthermore, these vaccines may modify the binding specificity of anti-PEG antibodies towards PEG-containing antigens.
Our research underscores the alteration of the anti-PEG antibody repertoire by PEGylated COVID-19 vaccines. This knowledge is particularly important before the use of a new PEG-containing therapeutic agents, as existing antibodies can not only reduce efficacy but also induce severe allergic-like reactions.
Project NO. 2023-2.1.2-KDP-2023-00016 has been implemented with the support provided by the Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund, financed under the KDP-2023 funding scheme.