Abstract

Background & Aims: Per- and polyfluoroalkyl substances (PFAS) are widely used, environmentally ubiquitous chemicals. Inhabitants in Ronneby, Sweden, have had long-term, moderate to high PFAS-exposure through drinking water contaminated by firefighting foams. PFAS has been associated with decreased vaccine-induced antibody responses in children. Effects in adults have been poorly investigated, in part owing to lack of well-designed trials of primary immunizations in PFAS exposed populations. The novelty of vaccination against COVID-19 and the associated clinical trials, offers a unique opportunity to investigate if PFAS decrease vaccine-induced antibody response in adults. Methods: Healthy, COVID-19 unvaccinated adults, 20-60 years old, from Ronneby (n=319; Perfluorooctanesulfonic acid (PFOS) median 46 ng/mL, range 1-543) and referents from neighboring Karlshamn (n=41; PFOS median 4 mg/mL, range 1-36), were vaccinated with two doses of the mRNA vaccine Spikevax® (Moderna). Seven PFAS were measured in serum before vaccination. Serum IgG antibodies against the spike antigen were measured before vaccination, and at five weeks (n=350) and six months (n=329) after the second vaccination. Regression analyses of antibodies were fitted against serum PFAS levels, quartile groups, smooth splines and between exposed and reference areas, adjusting for sex, age, smoking and previous SARS-CoV-2-infection. Results: Participants from Ronneby and referents had similar, high antibody levels (100% positive) five weeks and six months post vaccination, with waning levels over time. Regression models showed no clear pattern between antibody levels at five weeks or six months after vaccination and PFAS exposure. Results were replicated using different exposure indices, covariate adjustments and sensitivity analyses, and consistent for seven different PFAS compounds. Conclusions: In this clinical trial, with a wide PFAS exposure range and a low dropout rate, we assessed no indication that moderate to high PFAS exposure adversely affected antibody production in adults after COVID-19 mRNA vaccination. Keywords: PFAS, Immunotoxicity, Antibody, COVID-19 Vaccination

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