Evaluating PFAS-Induced modulation of peripheral blood mononuclear cells (PBMCs) immune response to SARS-CoV-2 spike in COVID-19 Vaccinees

The persistent nature of the environmental contaminants per- and polyfluoroalkyl substances (PFAS) has recently received considerable attention, particularly because of their adverse effects on immune system functionality in the context of vaccine responses to infectious diseases. Following COVID-19...

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Main Authors: Humblenoble Stembridge Ayuk, Arkadiusz Pierzchalski, Tamara Tal, Oddvar Myhre, Birgitte Lindeman, Nicola Margareta Smith, Violeta Stojanovska, Ana Claudia Zenclussen
Format: Article
Language:English
Published: Elsevier 2025-04-01
Series:Environment International
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Online Access:http://www.sciencedirect.com/science/article/pii/S0160412025001606
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author Humblenoble Stembridge Ayuk
Arkadiusz Pierzchalski
Tamara Tal
Oddvar Myhre
Birgitte Lindeman
Nicola Margareta Smith
Violeta Stojanovska
Ana Claudia Zenclussen
author_facet Humblenoble Stembridge Ayuk
Arkadiusz Pierzchalski
Tamara Tal
Oddvar Myhre
Birgitte Lindeman
Nicola Margareta Smith
Violeta Stojanovska
Ana Claudia Zenclussen
author_sort Humblenoble Stembridge Ayuk
collection DOAJ
description The persistent nature of the environmental contaminants per- and polyfluoroalkyl substances (PFAS) has recently received considerable attention, particularly because of their adverse effects on immune system functionality in the context of vaccine responses to infectious diseases. Following COVID-19 vaccination, some studies have shown a significant negative correlation between serum PFAS concentrations and the humoral immune response to the SARS-CoV-2 spike protein vaccination. However, the influence of PFAS on the cell-mediated immune response to SARS-CoV-2 spike protein post-COVID-19 vaccination remains underexplored. In the present study, we investigated the impact of a human blood-relevant PFAS mixture, containing perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) on innate (monocytes and NK cells), cell-mediated (T cells) and B cells adaptive immune responses in COVID-19-vaccinated female and male healthy donors. Human peripheral blood mononuclear cells (PBMCs) were exposed to a mixture of the six PFAS at real life concentrations and subsequently stimulated with the SARS-CoV-2 spike peptide. We report a significant upregulation of IFNγ production in T and NK cells, particularly among male donors exposed to high concentrations of the PFAS mixture. Conversely, we observed a decrease in the total B-cell population, particularly among female donors. A significant reduction in the secretion of the pro-inflammatory chemokines MIP-1α (CCL3) and MIP-3α (CCL20) was observed at high PFAS mixture concentrations. Overall, these findings suggest that high PFAS exposure may differentially affect immune responses in a sex-specific manner, with a potential impact on vaccine efficacy.
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spelling doaj-art-80815077f4b646b4bceb64f4a3a728032025-08-20T02:12:10ZengElsevierEnvironment International0160-41202025-04-0119810940910.1016/j.envint.2025.109409Evaluating PFAS-Induced modulation of peripheral blood mononuclear cells (PBMCs) immune response to SARS-CoV-2 spike in COVID-19 VaccineesHumblenoble Stembridge Ayuk0Arkadiusz Pierzchalski1Tamara Tal2Oddvar Myhre3Birgitte Lindeman4Nicola Margareta Smith5Violeta Stojanovska6Ana Claudia Zenclussen7Department of Environmental Immunology, Helmholtz Centre for Environmental Research, 04318 Leipzig, GermanyDepartment of Environmental Immunology, Helmholtz Centre for Environmental Research, 04318 Leipzig, GermanyDepartment of Ecotoxicology, Helmholtz Centre for Environmental Research, 04318 Leipzig, GermanyDepartment of Chemical Toxicology, Division of Climate and Environmental Health, Norwegian Institute of Public Health, PO Box PO Box 222 Skøyen, 0213 Oslo, NorwayDepartment of Chemical Toxicology, Division of Climate and Environmental Health, Norwegian Institute of Public Health, PO Box PO Box 222 Skøyen, 0213 Oslo, NorwayDepartment of Chemical Toxicology, Division of Climate and Environmental Health, Norwegian Institute of Public Health, PO Box PO Box 222 Skøyen, 0213 Oslo, NorwayDepartment of Environmental Immunology, Helmholtz Centre for Environmental Research, 04318 Leipzig, GermanyDepartment of Environmental Immunology, Helmholtz Centre for Environmental Research, 04318 Leipzig, Germany; Saxon Incubator for Translational Research, University of Leipzig, 04103 Leipzig, Germany; German Center for Child and Adolescent Health (DZKJ), partner site Leipzig, Dresden, Germany; Corresponding author at: Department of Environmental Immunology, Helmholtz Centre for Environmental Research - UFZ, Permoserstrasse 15, 04318 Leipzig, Germany.The persistent nature of the environmental contaminants per- and polyfluoroalkyl substances (PFAS) has recently received considerable attention, particularly because of their adverse effects on immune system functionality in the context of vaccine responses to infectious diseases. Following COVID-19 vaccination, some studies have shown a significant negative correlation between serum PFAS concentrations and the humoral immune response to the SARS-CoV-2 spike protein vaccination. However, the influence of PFAS on the cell-mediated immune response to SARS-CoV-2 spike protein post-COVID-19 vaccination remains underexplored. In the present study, we investigated the impact of a human blood-relevant PFAS mixture, containing perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) on innate (monocytes and NK cells), cell-mediated (T cells) and B cells adaptive immune responses in COVID-19-vaccinated female and male healthy donors. Human peripheral blood mononuclear cells (PBMCs) were exposed to a mixture of the six PFAS at real life concentrations and subsequently stimulated with the SARS-CoV-2 spike peptide. We report a significant upregulation of IFNγ production in T and NK cells, particularly among male donors exposed to high concentrations of the PFAS mixture. Conversely, we observed a decrease in the total B-cell population, particularly among female donors. A significant reduction in the secretion of the pro-inflammatory chemokines MIP-1α (CCL3) and MIP-3α (CCL20) was observed at high PFAS mixture concentrations. Overall, these findings suggest that high PFAS exposure may differentially affect immune responses in a sex-specific manner, with a potential impact on vaccine efficacy.http://www.sciencedirect.com/science/article/pii/S0160412025001606PFAS mixturesPFAS exposureSevere Acute Respiratory Coronavirus (SARS-CoV-2)Spike proteinperipheral blood mononuclear cells (PBMCs)COVID-19 vaccination
spellingShingle Humblenoble Stembridge Ayuk
Arkadiusz Pierzchalski
Tamara Tal
Oddvar Myhre
Birgitte Lindeman
Nicola Margareta Smith
Violeta Stojanovska
Ana Claudia Zenclussen
Evaluating PFAS-Induced modulation of peripheral blood mononuclear cells (PBMCs) immune response to SARS-CoV-2 spike in COVID-19 Vaccinees
Environment International
PFAS mixtures
PFAS exposure
Severe Acute Respiratory Coronavirus (SARS-CoV-2)
Spike protein
peripheral blood mononuclear cells (PBMCs)
COVID-19 vaccination
title Evaluating PFAS-Induced modulation of peripheral blood mononuclear cells (PBMCs) immune response to SARS-CoV-2 spike in COVID-19 Vaccinees
title_full Evaluating PFAS-Induced modulation of peripheral blood mononuclear cells (PBMCs) immune response to SARS-CoV-2 spike in COVID-19 Vaccinees
title_fullStr Evaluating PFAS-Induced modulation of peripheral blood mononuclear cells (PBMCs) immune response to SARS-CoV-2 spike in COVID-19 Vaccinees
title_full_unstemmed Evaluating PFAS-Induced modulation of peripheral blood mononuclear cells (PBMCs) immune response to SARS-CoV-2 spike in COVID-19 Vaccinees
title_short Evaluating PFAS-Induced modulation of peripheral blood mononuclear cells (PBMCs) immune response to SARS-CoV-2 spike in COVID-19 Vaccinees
title_sort evaluating pfas induced modulation of peripheral blood mononuclear cells pbmcs immune response to sars cov 2 spike in covid 19 vaccinees
topic PFAS mixtures
PFAS exposure
Severe Acute Respiratory Coronavirus (SARS-CoV-2)
Spike protein
peripheral blood mononuclear cells (PBMCs)
COVID-19 vaccination
url http://www.sciencedirect.com/science/article/pii/S0160412025001606
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