Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1784862757335597056 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9807604 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT quanpaolaleonor sarscov2vaccineexcipientspolyethyleneglycolandtrometamoldonotinducemastcelldegranulationinaninvitromodelfornonigemediatedhypersensitivity AT ollelaia sarscov2vaccineexcipientspolyethyleneglycolandtrometamoldonotinducemastcelldegranulationinaninvitromodelfornonigemediatedhypersensitivity AT sabatebrescomarina sarscov2vaccineexcipientspolyethyleneglycolandtrometamoldonotinducemastcelldegranulationinaninvitromodelfornonigemediatedhypersensitivity AT guoyanru sarscov2vaccineexcipientspolyethyleneglycolandtrometamoldonotinducemastcelldegranulationinaninvitromodelfornonigemediatedhypersensitivity AT munozcanorosa sarscov2vaccineexcipientspolyethyleneglycolandtrometamoldonotinducemastcelldegranulationinaninvitromodelfornonigemediatedhypersensitivity AT wagnerannette sarscov2vaccineexcipientspolyethyleneglycolandtrometamoldonotinducemastcelldegranulationinaninvitromodelfornonigemediatedhypersensitivity AT gastaminzagabriel sarscov2vaccineexcipientspolyethyleneglycolandtrometamoldonotinducemastcelldegranulationinaninvitromodelfornonigemediatedhypersensitivity AT martinmargarita sarscov2vaccineexcipientspolyethyleneglycolandtrometamoldonotinducemastcelldegranulationinaninvitromodelfornonigemediatedhypersensitivity |