Theoretical and Translational Medicine 4.
Ms. Facskó, Réka, MSc
Institute of Clinical Pathophysiology, Semmelweis University
305771548
facsko.reka@semmelweis.hu
Affinity Maturation and Specificity Shifts in Anti-PEG Antibodies Induced by mRNA-LNP Vaccines
Réka Facskó1, Tamás Mészáros1, János Szebeni1, Gergely Tibor Kozma1
1: Nanomedicine Research and Education Center, Institute of Clinical Pathophysiology, Semmelweis University, Budapest, Hungary
Szóbeli
Theoretical and Translational Medicine 4.
English
Theoretical and Translational Medicine
Polyethylene glycols (PEG) and polysorbates (e.g., PS80, PS20) are synthetic polymers composed of repeating oxyethylene units. PS80 is used as an emulsifier and stabilizer in adenoviral vector COVID-19 vaccines, such as AstraZeneca, Sputnik V and Janssen, whereas PEG2000 is covalently attached to lipid nanoparticle (LNP) formulations, as used in Comirnaty and Spikevax. Following vaccination with LNP‑based COVID-19 vaccines, several studies have reported significant increases in both anti-PEG IgM and IgG antibody levels, potentially amplifying PEG-related adverse immune effects. Because of their structural similarity, antibodies against PEG and polysorbates are often highly cross-reactive.
We sought to characterize vaccine-induced changes in the specificity of poly(oxyethylene)‑reactive antibodies and the avidity of anti-PEG IgG antibodies following immunization with PEG- and polysorbate-containing COVID-19 vaccines. Quantitative ELISAs were used to characterize anti-PEG and anti-PS IgM and IgG responses in 353 samples. Equilibrium titration ELISAs were applied to assess IgG binding to PEG molecules, micelles, and PEGylated liposomes in 36 samples.
PEGylated LNP vaccines (especially Spikevax) increased both PEG- and PS-specific antibody levels, with a shift toward greater PEG specificity. Anti-PEG antibodies exhibited higher avidity for larger PEGylated structures, from free PEG molecules through PEG micelles to PEGylated liposomes. Following Comirnaty and Spikevax vaccination, anti-PEG antibodies showed significantly increased avidity for nearly all PEG-containing competitor antigens. Additionally, a shorter poly(oxyethylene) segment was sufficient for binding by vaccine-induced anti-PEG IgG compared with pre-existing antibodies present in unvaccinated control subjects.
In summary, PEGylated LNP vaccines reshaped the anti-PEG antibody repertoire and induced the formation of end-group-specific anti-PEG antibodies. As a result of the widespread use of PEG-containing COVID-19 vaccines, the anti-PEG antibody profile of the current population may differ from that observed prior to their introduction.
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.
Semmelweis University
Gergely Tibor Kozma
I do not give consent to the publication of my abstract on the website of the congress.
after finishing doctoral studies with absolutorium (PhD)
Szabad
elfogadva
szóbeli
nem rendelkezett róla
8004
16:00
16:10