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University of California-Berkeley

Superfund Research Program

Influence of Exposure to a Mixture of PFAS and Metals on the Developing Immune System

Project Leader: Andres Cardenas (Stanford University)
Co-Investigator: Joseph August Lewnard
Grant Number: P42ES004705
Funding Period: 2022-2027
View this project in the NIH Research Portfolio Online Reporting Tools (RePORT)

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Project Summary (2022-2027)

Early-life exposures, both prenatally and in early childhood, can lead to lasting consequences in the development of health and disease throughout the life-course. Two major classes of ubiquitous chemicals detected almost universally across human populations are metals and synthetic per- and polyfluoroalkyl substances (PFAS). Metals and metalloids, such as lead and arsenic, are known hazardous substances and prenatal exposure has been shown to modulate the developing immune system. Similarly, exposure to PFAS consistently has been associated with decreased immune response to important childhood immunizations like the tetanus and diphtheria vaccines. However, the understanding of the combined impact of these two classes of chemicals on the developing immune system and immune response remains limited. While childhood immunization remains a cornerstone for public health prevention the understanding on how early-life chemical exposures affect immune system development and response remains extremely limited. Even more limited is an understanding of the joint contribution of multiple chemical exposures in early life on the immune system. Current risk assessments for these compounds are performed with adult endpoints and estimates of exposure to a single chemical.

This project is comprehensively and systematically investigating the influence of prenatal and early-life exposure to a mixture of metals and PFAS on the developing immune system and their influence on vaccine-induced immunity. The project researchers are leveraging specimens from Project Viva, a prospective birth cohort recruited in Boston, Massachusetts, to

  • Determine if a prenatal mixture of first trimester metals and PFAS are individually and jointly associated as a mixture with cord blood cytokines and lymphocyte proliferation at birth;
  • Quantify the extent to which a prenatal metal/PFAS mixture is associated with tetanus, diphtheria and pertussis (TDAP) and measles, mumps, and rubella (MMR) vaccine titers in mid-childhood (7 years of age) and evaluate the extent to which postnatal childhood metal and PFAS exposure contributes to this relationship; and
  • Test if DNA methylation signatures at birth measured in leukocytes mediate associations between prenatal chemical exposure and reduced TDAP and MMR vaccine antibody response in childhood.

In this project, the team is testing longitudinal associations in a large cohort of mother-child pairs with detailed confounder information and existing high-quality data and samples. They are implementing novel statistical methodology to test different prenatal and postnatal environmental mixtures to comprehensively quantify the impact of chemical exposures on the developing immune system and vaccine-induced immunity. This project provides critical knowledge on the developmental immunotoxicity of PFAS and metals, individually and as a mixture, at environmentally relevant concentrations for the U.S. population. The immune parameters of this research are clinically relevant and will help inform risk assessments for individuals as well as public health guidelines with the goal of protecting children.

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