Poster Session III. - K: Theoretical and Translational Medicine
Facskó Réka, MSc
UN9JFD
Nanomedicine Research and Education Center, Department of Translational Medicine, Semmelweis University, Budapest, Hungary
+36305771548
facsko.reka@phd.semmelweis.hu
Indications of Anti-PEG Memory-like B Cell Activity After mRNA-LNP COVID-19 Vaccination
Réka Facskó1,2,3, Tamás Mészáros1,2,3, János Szebeni1,3, Tibor Gergely Kozma1,3
1: Nanomedicine Research and Education Center, Department of Translational Medicine, Semmelweis University, Budapest, Hungary
2: Heart and Vascular Center, Semmelweis University, Budapest, Hungary
3: SeroScience LCC, Budapest, Hungary
Poszter
Poster Session III. - K: Theoretical and Translational Medicine
English
Theoretical and Translational Medicine
Since the introduction of PEG-containing mRNA-lipid nanoparticle (LNP)-based Covid-19 vaccines, several studies have independently reported a significant increase in anti-PEG IgM and IgG antibodies following vaccination with Spikevax, Comirnaty or both. According to current knowledge, both vaccines induce a thymus-independent type 2 (TI-2) immune response against PEG. While TI-2 responses are traditionally not associated with immunological memory, some data indicate that they may generate memory-like B cells capable of producing high-affinity antibodies upon re-exposure to PEG antigens.
In this study, we investigated the presence and reactivation potential of anti-PEG memory-like B cells in the peripheral blood of individuals who received LNP-based Covid-19 vaccines.
Freshly isolated PBMCs were analysed for unswitched memory B cells (CD19+/CD27+/IgM+), switched memory B cells (CD19+/CD27+/IgM-) and naive B cells (CD19+/CD27-/IgM+) using flow cytometry, assessing their ability to bind fluorescently labelled PEG molecules and PEG-containing liposomes. To evaluate reactivation potential, PBMCs were stimulated in vitro using specific (DSPE-PEG micelles, PEGylated liposomes) and nonspecific (TLR agonists and cytokines) activation signals. Anti-PEG antibody secretion was measured in culture supernatants at multiple time points by ELISA.
We found that PEG alone was insufficient to detect PEG-specific B cells, likely due to inadequate BCR cross-linking. However, liposome-based labelling allowed identification of B cells with potential PEG reactivity, although specificity could not be confirmed. Additionally, we established a method using a combination of nonspecific activation signals that induced measurable anti-PEG IgM secretion in 5-day culture supernatants.
Our results suggest that PEG-reactive memory-like B cells may persist post-vaccination and can be reactivated in vitro, potentially contributing to anti-PEG antibody production upon future PEG exposure. This reactivation could pose a risk of reduced therapeutic efficacy or even serious adverse immune reactions following administration of PEGylated drugs.
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
Tibor Gergely Kozma
I do not give consent to the publication of my abstract on the website of the congress.
in doctoral studies after complex exam (PhD)
Szabad
elfogadva
poszter
nem rendelkezett róla
8004
14:36
14:42