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 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.