Per- and polyfluoroalkyl substances, commonly known as PFAS, have become a focal point of concern in environmental health research due to their widespread presence and persistence in the environment. These synthetic compounds are found in an array of consumer products including cosmetics, outdoor apparel, and non-stick cookware. Their unique chemical properties—resistance to heat, water, and grease—have led to their pervasive use in industry and everyday life. However, these same properties also make PFAS remarkably resistant to degradation, earning them the nickname “forever chemicals.” They accumulate in the soil, air, and water, infiltrating ecosystems and biological systems worldwide.
Exposure to PFAS poses significant challenges, especially because they enter the human body through various pathways including contaminated food, drinking water, and air. While these compounds are not acutely toxic, chronic exposure is nearly unavoidable in modern societies. This sustained presence and bioaccumulation raise serious concerns about long-term health outcomes, particularly in vulnerable subpopulations such as pregnant women, young children, and individuals with chronic illnesses. Such groups may experience heightened risks due to the subtle but persistent effects of these chemicals.
Scientific investigations have uncovered associations between PFAS exposure and several detrimental health conditions, including metabolic disorders like obesity, disruptions in hormonal balance, and increased cancer risk. Beyond these effects, PFAS are now recognized as modulators of the immune system, a revelation that carries significant implications for public health. Recent epidemiological data highlight how PFAS compromise immune responses, notably by dampening antibody production following vaccination against infectious diseases, with SARS-CoV-2 being a prominent example.
Understanding the intricacies of the immune system’s response to PFAS exposure is critical, especially given the ongoing global challenges posed by COVID-19. Immunity against SARS-CoV-2 involves both humoral immunity mediated by antibodies and cellular immunity driven by T cells and other immune components. While antibody levels have traditionally been used as a marker of vaccine effectiveness, they do not tell the entire story. The cellular arm of the immune response is equally vital for protection against severe infections but has been less studied in the context of PFAS exposure.
Addressing this knowledge gap, a collaborative research team led by Professor Ana Zenclussen from the Helmholtz Centre for Environmental Research (UFZ) conducted an in-depth experimental study focused on how PFAS influence cellular immune responses in individuals vaccinated against SARS-CoV-2. By isolating peripheral blood mononuclear cells (PBMCs) from vaccinated individuals with prior COVID-19 infection, the researchers were able to meticulously examine immune cell behavior when exposed to PFAS in laboratory conditions. This approach allowed for controlled analyses of direct effects, bypassing the complexity of whole-body interactions that often obscure mechanistic insights.
Central to the study’s design was the use of a PFAS mixture carefully calibrated to mimic real-world exposure levels observed across European populations. This mixture was developed in collaboration with Norwegian partners from the Institute of Public Health in Oslo and was derived from extensive cohort data to ensure ecological validity. To explore dose-dependent effects, the immune cells were also subjected to PFAS concentrations up to a thousand times higher, simulating exposure scenarios relevant to workers in PFAS production facilities.
Following a 24-hour incubation with the PFAS mixture, the PBMCs were then stimulated with SARS-CoV-2 spike proteins to evaluate their immune responsiveness. Cutting-edge spectral flow cytometry was employed to dissect the immune cell repertoire with high resolution, enabling quantification and identification of multiple immune subsets within a single assay. This technology also facilitated the measurement of cytokines and chemokines—immune signaling molecules that dictate cell communication and functional responses.
The results painted a nuanced and concerning picture. At elevated PFAS concentrations, two distinct types of immune cells displayed an exaggerated inflammatory response when re-exposed to SARS-CoV-2 antigens. This phenomenon, characterized by increased secretion of inflammatory mediators, suggests a dysregulated immune activation that may have harmful consequences if replicated in vivo. Intriguingly, this hyperinflammatory trend was markedly more pronounced in the samples derived from male participants, hinting at potential sex-specific vulnerabilities.
Conversely, female participants’ immune cells exhibited a different pattern. Higher PFAS exposure correlated with a reduction in B cell populations, the specialized lymphocytes responsible for producing antibodies and sustaining long-term immunity. Such depletion could undermine humoral immune memory and impair vaccine efficacy, raising important questions about sex-based differences in immune modulation by environmental contaminants.
Moreover, the production of key soluble immune mediators involved in recruiting other immune cells to the site of infection and in tissue repair processes was adversely affected across both sexes. These functional impairments further underscore the potential for PFAS to not only skew immune responses but also impede the resolution phase of inflammation, which is critical for restoring tissue homeostasis after viral challenges.
Collectively, these findings underscore the complexity of PFAS-induced immunomodulation and highlight the potential public health ramifications. Individuals experiencing high PFAS burdens—whether occupationally or environmentally—might face increased risks of suboptimal vaccine responses and more severe disease progression if infected with SARS-CoV-2 or similar pathogens. Tailoring vaccination strategies to account for such environmental exposures could become an essential component of personalized medicine and epidemiological planning.
Professor Ana Zenclussen emphasized the significance of these discoveries, noting that this research fills a crucial gap in understanding how chronic environmental pollutants alter cellular immunity. The sex-differentiated effects warrant further investigation to inform risk assessments and public health interventions that consider biological variability.
Dr. Oddvar Myhre of the Norwegian Institute of Public Health highlighted the methodological strengths of the study, particularly the use of human-relevant PFAS mixtures reflective of actual exposure scenarios. This approach moves beyond single-compound toxicology, embracing the complex interactions found in real-world PFAS contamination and its health consequences.
As PFAS contamination continues to be a pressing environmental and health issue globally, studies like this provide critical mechanistic insights that bridge laboratory findings with epidemiological trends. The integration of advanced immunological techniques, realistic exposure models, and interdisciplinary collaboration marks a new frontier in assessing how “forever chemicals” impact human health at the immune system level.
Future research directions should include long-term cohort studies tracking PFAS exposure alongside vaccine responsiveness and infection outcomes, stratified by sex and other demographic factors. Intervention strategies to reduce PFAS exposure and mitigate its immunotoxic effects should also be prioritized to protect vulnerable populations and enhance global health resilience.
Subject of Research: Cells
Article Title: Evaluating PFAS-Induced modulation of peripheral blood mononuclear cells (PBMCs) immune response to SARS-CoV-2 spike in COVID-19 Vaccinees
News Publication Date: 26-Mar-2025
Web References: 10.1016/j.envint.2025.109409
Keywords
PFAS, immune modulation, SARS-CoV-2, COVID-19 vaccination, cellular immunity, peripheral blood mononuclear cells, spectral flow cytometry, sex differences, environmental contaminants, chronic exposure, immunotoxicity, antibody response
