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Development of a novel translational porcine model of Ascaris-induced chronic lung disease.

Award Number: R03AI180714
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2023
PERIOD OF PERFORMANCE END DATE: 10/31/2025

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Development of a novel translational porcine model of Ascaris-induced chronic lung disease. - PROJECT SUMMARY/ABSTRACT Ascaris (roundworm) is the most prevalent helminth in the world infecting millions of people living in poverty- stricken, parasite-endemic regions in low- and middle-income countries (LMICs). Ascaris infects children early in life and has a highly immunogenic larval migratory phase through the lungs before returning to the intestines and developing into adult worms. High Ascaris worm burden and significant re-infection rates in children causes profound life-long morbidity. Using our Ascaris mouse model, our lab discovered that transient Ascaris larval migration through the lungs leads to chronic structural and functional changes consistent chronic lung disease. Chronic lung disease in the mouse model was associated with sustained concentrations of Th2 and Th17 cells in the lungs suggesting on-going immune activation despite infection resolution. The data suggest Ascaris may be a contributing risk factor for the development of chronic lung disease in parasite-endemic areas. However, despite our robust Ascaris mouse model findings, mice are a non-native host for ascariasis. Evaluating Ascaris- induced chronic lung disease in human clinical trials is ideal but challenging due to the complexity of the parasitic life cycle and the lack of sustainable long-term resources in parasite-endemic regions. In addition to humans, domestic pigs are a native host for Ascaris spp. Additionally, due to similar lung anatomy, physiology and immunologic responses pigs are used routinely as animal models of human disease. Furthermore, like human ascariasis, Ascaris is the most prevalent helminth infection in pigs and has significant consequences on porcine health. The overall objective of this proposal is to develop a novel, translational porcine model of ascariasis to evaluate the long-term consequences of Ascaris larval migration through the native host lungs. We hypothesize that Ascaris larval migration through the lungs of a native host will cause Ascaris-induced chronic lung disease. The first aim will evaluate the impact of Ascaris larval migration on lung function and structure longitudinally in a porcine model. We will use human grade physiologic monitoring systems and histopathology to determine Ascaris-induced chronic lung disease. In the second aim we will characterize the immunologic milieu in the lungs longitudinally following Ascaris larval migration in a porcine model. Using immunologic assays and RNA sequencing we will identify key immunologic pathways involved in Ascaris-induced chronic lung disease. This “One Health” model will provide important information regarding the impact of Ascaris larval migration on both humans and pigs, leading to improved health within the shared environment. Our findings will be used to identify novel therapeutic targets to prevent ascariasis in both humans and pigs in parasite-endemic regions globally.


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 = $77,843 )
2025	2025	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Allergy and Infectious Diseases Research	000	2	11/5/2024	NON-COMPETING CONTINUATION	$77,843
														Subtotal = $77,843

Issue Date FY: 2024 ( Subtotal = $80,250 )
2024	2024	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Allergy and Infectious Diseases Research	001	1	9/11/2024	NEW	$8,025
2024	2024	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Allergy and Infectious Diseases Research	000	1	12/1/2023	NEW	$72,225
														Subtotal = $80,250

Grand Total All Awards = $158,093

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Development of a novel translational porcine model of Ascaris-induced chronic lung disease.

Award Number: R03AI180714

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/01/2023

PERIOD OF PERFORMANCE END DATE: 10/31/2025

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