# Early-life metal exposures, mitochondrial heteroplasmy, and child antibody response to vaccination

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $609,805

## Abstract

SUMMARY
Individual responses to vaccinations are a critical public health issue and mounting evidence suggests that
early life environmental factors may program immune dysregulation that manifests years later. This
developmental origins of health and development (DOHaD) theory posits that dose and timing of early life
immunotoxic environmental exposures can have long-lasting consequences on the trajectory of immune
system function. The immune system begins to develop in utero and, as children age and experience
infections and vaccinations, an ever-expanding repertoire of antibodies become part of their lifelong immune
memory. Yet research on child immune function and its response to ubiquitous immunotoxic metal
exposures—experienced in utero and early in life (0–5 years)—has been largely overlooked.We will address
this knowledge gap in the Mexican PROGRESS study, which has measures of immunotoxic metal exposures
[arsenic (As), cadmium (Cd), manganese (Mn), and lead (Pb)] at several key developmental time windows and
from multiple biomatrices (tooth, blood, and urine). We will assess child immune function by measuring
antibody levels at 4, 6, 8, 10–11, and 13–15 years of age in response to scheduled childhood vaccinations
(i.e., measles, mumps, rubella, diphtheria, tetanus, and pertussis). Our preliminary data show that (i) exposure
to individual metals (Cd, Pb) and a metal mixture (As, Cd, Mn, Pb) may result in poorer antibody responses at
age 4 years and that (ii) there are critical windows of susceptibility to As, Mn, and Pb exposures. Additionally,
metal exposures induce systemic oxidative stress (OS) leading to suboptimal immune system function. Given
the pro-oxidant role of metals, we will also quantify cumulative OS via a novel biomarker—mitochondrial DNA
(mtDNA) heteroplasmy, which reflects OS-induced mtDNA mutation counts accumulating over time. Our initial
data show that prenatal metal exposures are associated with mtDNA heteroplasmy counts at birth. We will
measure mtDNA heteroplasmy at birth and at 8 and 13–15 years of age as a predictor and mediator of
antibody responses. In Aim 1, we will determine the association between exposure to individual metals and
metal mixtures with child antibody responses to vaccination at specific ages and antibody response trajectories
over time. In Aim 2, we will determine critical windows of susceptibility to immunotoxic metals exposure on
child immune system at specific ages and over time. In Aim 3, we will investigate associations between mtDNA
heteroplasmy levels and (i) exposure to individual metals and metal mixtures and (ii) child antibody response to
vaccination at specific ages and antibody response trajectories. We will apply statistical causal modeling
strategies to evaluate the mediating role of mitochondrial biomarkers on the metal–immune system
relationship. Completion of these aims will drive interventions that may help prevent lifelong immune system
dysregulation and related adverse heal...

## Key facts

- **NIH application ID:** 10512528
- **Project number:** 1R01ES034521-01
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Elena Colicino
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $609,805
- **Award type:** 1
- **Project period:** 2022-09-08 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10512528

## Citation

> US National Institutes of Health, RePORTER application 10512528, Early-life metal exposures, mitochondrial heteroplasmy, and child antibody response to vaccination (1R01ES034521-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10512528. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*