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SARS-CoV-2 vaccine excipients polyethylene glycol and trometamol do not induce mast cell degranulation, in an in vitro model for non-IgE-mediated hypersensitivity

The development of vaccines against SARS-CoV2 brought about several challenges, including the management of hypersensitivity reactions to these formulations. The search for underlying mechanisms involved in these adverse events initially focused on excipients which may trigger mast cell activation r...

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Autores principales: Quan, Paola Leonor, Ollé, Laia, Sabaté-Brescó, Marina, Guo, Yanru, Muñoz-Cano, Rosa, Wagner, Annette, Gastaminza, Gabriel, Martín, Margarita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9807604/
https://www.ncbi.nlm.nih.gov/pubmed/36606064
http://dx.doi.org/10.3389/falgy.2022.1046545
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author Quan, Paola Leonor
Ollé, Laia
Sabaté-Brescó, Marina
Guo, Yanru
Muñoz-Cano, Rosa
Wagner, Annette
Gastaminza, Gabriel
Martín, Margarita
author_facet Quan, Paola Leonor
Ollé, Laia
Sabaté-Brescó, Marina
Guo, Yanru
Muñoz-Cano, Rosa
Wagner, Annette
Gastaminza, Gabriel
Martín, Margarita
author_sort Quan, Paola Leonor
collection PubMed
description The development of vaccines against SARS-CoV2 brought about several challenges, including the management of hypersensitivity reactions to these formulations. The search for underlying mechanisms involved in these adverse events initially focused on excipients which may trigger mast cell activation responses via non-IgE pathways: polyethylene glycol and trometamol. We sought to determine whether these components, in their pure form, were capable of stimulating mast cells directly. To test this hypothesis, we used an in vitro model for non-IgE-mediated activation that has previously shown degranulation responses induced via MRGPRX2 with known drug agonists of the receptor. Human LAD2 mast cells were incubated with different concentrations (1, 10, 50 mg/ml) of trometamol and of purified polyethylene glycol/Macrogol (molecular weights: 2,000, 3,350, 4,000, and 6,000). Mast cell degranulation was assessed using a beta-hexosaminidase read-out. Interestingly, degranulation responses for all reagents tested showed no significant differences from those obtained from the negative control (basal degranulation). Receptor-silencing assays were therefore not conducted. In summary, purified PEG and trometamol did not induce mast cell degranulation in this in vitro model for the study of non-IgE mechanisms of drug hypersensitivity, previously shown to be useful in the investigation of MRGPRX2 ligands. Studies using complete vaccine formulations, lipid conjugates, and receptor gene variants are needed to further clarify mechanisms of vaccine hypersensitivity.
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spelling pubmed-98076042023-01-04 SARS-CoV-2 vaccine excipients polyethylene glycol and trometamol do not induce mast cell degranulation, in an in vitro model for non-IgE-mediated hypersensitivity Quan, Paola Leonor Ollé, Laia Sabaté-Brescó, Marina Guo, Yanru Muñoz-Cano, Rosa Wagner, Annette Gastaminza, Gabriel Martín, Margarita Front Allergy Allergy The development of vaccines against SARS-CoV2 brought about several challenges, including the management of hypersensitivity reactions to these formulations. The search for underlying mechanisms involved in these adverse events initially focused on excipients which may trigger mast cell activation responses via non-IgE pathways: polyethylene glycol and trometamol. We sought to determine whether these components, in their pure form, were capable of stimulating mast cells directly. To test this hypothesis, we used an in vitro model for non-IgE-mediated activation that has previously shown degranulation responses induced via MRGPRX2 with known drug agonists of the receptor. Human LAD2 mast cells were incubated with different concentrations (1, 10, 50 mg/ml) of trometamol and of purified polyethylene glycol/Macrogol (molecular weights: 2,000, 3,350, 4,000, and 6,000). Mast cell degranulation was assessed using a beta-hexosaminidase read-out. Interestingly, degranulation responses for all reagents tested showed no significant differences from those obtained from the negative control (basal degranulation). Receptor-silencing assays were therefore not conducted. In summary, purified PEG and trometamol did not induce mast cell degranulation in this in vitro model for the study of non-IgE mechanisms of drug hypersensitivity, previously shown to be useful in the investigation of MRGPRX2 ligands. Studies using complete vaccine formulations, lipid conjugates, and receptor gene variants are needed to further clarify mechanisms of vaccine hypersensitivity. Frontiers Media S.A. 2022-12-20 /pmc/articles/PMC9807604/ /pubmed/36606064 http://dx.doi.org/10.3389/falgy.2022.1046545 Text en © 2022 Quan, Ollé, Sabaté-Brescó, Guo, Muñoz-Cano, Wagner, Gastaminza and Martín. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (https://creativecommons.org/licenses/by/4.0/) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Allergy
Quan, Paola Leonor
Ollé, Laia
Sabaté-Brescó, Marina
Guo, Yanru
Muñoz-Cano, Rosa
Wagner, Annette
Gastaminza, Gabriel
Martín, Margarita
SARS-CoV-2 vaccine excipients polyethylene glycol and trometamol do not induce mast cell degranulation, in an in vitro model for non-IgE-mediated hypersensitivity
title SARS-CoV-2 vaccine excipients polyethylene glycol and trometamol do not induce mast cell degranulation, in an in vitro model for non-IgE-mediated hypersensitivity
title_full SARS-CoV-2 vaccine excipients polyethylene glycol and trometamol do not induce mast cell degranulation, in an in vitro model for non-IgE-mediated hypersensitivity
title_fullStr SARS-CoV-2 vaccine excipients polyethylene glycol and trometamol do not induce mast cell degranulation, in an in vitro model for non-IgE-mediated hypersensitivity
title_full_unstemmed SARS-CoV-2 vaccine excipients polyethylene glycol and trometamol do not induce mast cell degranulation, in an in vitro model for non-IgE-mediated hypersensitivity
title_short SARS-CoV-2 vaccine excipients polyethylene glycol and trometamol do not induce mast cell degranulation, in an in vitro model for non-IgE-mediated hypersensitivity
title_sort sars-cov-2 vaccine excipients polyethylene glycol and trometamol do not induce mast cell degranulation, in an in vitro model for non-ige-mediated hypersensitivity
topic Allergy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9807604/
https://www.ncbi.nlm.nih.gov/pubmed/36606064
http://dx.doi.org/10.3389/falgy.2022.1046545
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