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Vulnerability During Infancy to Immunotoxic Contaminant Exposures

Award Number: R01ES030394
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2020
PERIOD OF PERFORMANCE END DATE: 01/31/2026

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Vulnerability During Infancy to Immunotoxic Contaminant Exposures - Abstract Our studies have demonstrated that developmental exposure to perfluorinated alkylate substances (PFAS) are associated with attenuated antibody responses to routine childhood vaccines. Our most recent findings suggest that breastfeeding can transfer PFAS to the infant and lead to substantial elevations of serum-PFAS concentrations, with possible adverse implications for immune system development. As blood samples from infancy were not available to us in previous studies, we modeled the concentrations of early-life serum-PFAS and showed that levels of early postnatal serum-PFAS are inversely associated with antibody concentrations measured at age 5 years, more so than serum concentrations measured at age 18 months or later. The present proposal will obtain blood samples in infancy and maternal milk for analysis of PFAS to improve the modeling of profiles of serum-PFAS during infancy. This will allow testing of the hypothesis that early-life exposure to immunotoxic PFAS impair the development of the adaptive immune system and negatively affects the efficacy of routine childhood vaccines. The extended model of serum-PFAS will be used for estimation of exposures of PFAS in infancy among >1,000 children from previous cohorts, where serum samples from infancy were not collected. In addition to blood sampling at ages 3 and 12 months in the new cohort, we will use novel cell phone technology to allow mothers to record breastfeeding, occurrence of infectious disease, antibiotic treatment, and other relevant study parameters every two weeks. Our focus on vaccines will include toxoids (diphtheria and tetanus), as these de novo protein vaccines are known to be the most reliable clinical indicators of immune suppression. The duration of breastfeeding will be considered both as an exposure pathway and a moderator, as breastfeeding is considered to be advantageous for the child’s immune system development. The proposed study will be carried out at the Faroe Islands, where excellent conditions are available to recruit the birth cohort and to ensure a high participation rate and minimal socioeconomic confounding. Exposures of PFAS mainly originate from seafood and vary substantially, while average serum concentrations are similar to U.S. levels. A cohort size of 600 can be recruited within 16 months and will provide appropriate statistical power as one of the largest so far in the field. At 3 and 12 months of age, vaccine antibodies, thymus size, and advanced differential white cell counts will be assessed. Statistical data analysis will include multivariate analysis, assessment of mediation and/or modulation, structural equation modeling of combined exposure of exposure associations of PFAS with immune functions, and benchmark dose calculations. While research on immunotoxicology has traditionally focused on adverse effects in the mature organism, this proposal aims to characterize immunotoxic risks from developmental exposure to these priority pollutants at the most vulnerable developmental stages in early life.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2023	SYDDANSK UNIVERSITET (UNIVERSITY OF SOUTHERN DENMARK)	CAMPUSVEJ 55	ODENSE M				DNK	Environmental Health	000	4	2/13/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	SYDDANSK UNIVERSITET (UNIVERSITY OF SOUTHERN DENMARK)	CAMPUSVEJ 55	ODENSE M				DNK	Environmental Health	002	4	10/16/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$855,662
2024	2022	HARVARD COLLEGE PRESIDENT & FELLOWS OF	677 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Environmental Health	001	3	10/16/2023	NON-COMPETING CONTINUATION	-$531,842
2024	2021	HARVARD COLLEGE PRESIDENT & FELLOWS OF	677 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Environmental Health	000	2	10/16/2023	NON-COMPETING CONTINUATION	-$323,820
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $364,949 )
2023	2023	SYDDANSK UNIVERSITET (UNIVERSITY OF SOUTHERN DENMARK)	CAMPUSVEJ 55	ODENSE M				DNK	Environmental Health	001	4	3/9/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$364,949
2023	2022	HARVARD COLLEGE PRESIDENT & FELLOWS OF	677 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Environmental Health	000	3	3/8/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $364,949

Issue Date FY: 2022 ( Subtotal = $531,842 )
2022	2022	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	677 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Environmental Health	000	3	1/21/2022	NON-COMPETING CONTINUATION	$531,842
														Subtotal = $531,842

Issue Date FY: 2021 ( Subtotal = $515,620 )
2021	2021	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	677 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Environmental Health	000	2	2/1/2021	NON-COMPETING CONTINUATION	$515,620
														Subtotal = $515,620

Issue Date FY: 2020 ( Subtotal = $538,523 )
2020	2020	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	677 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Environmental Health	001	1	7/24/2020	NEW	$0
2020	2020	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	677 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Environmental Health	000	1	3/31/2020	NEW	$538,523
														Subtotal = $538,523

Grand Total All Awards = $1,950,934

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Vulnerability During Infancy to Immunotoxic Contaminant Exposures

Award Number: R01ES030394

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/01/2020

PERIOD OF PERFORMANCE END DATE: 01/31/2026

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