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Maternal effect on offspring immunity against hepatitis B virus

Award Number: R01AI145813
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: 07/03/2019
PERIOD OF PERFORMANCE END DATE: 06/30/2024

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Maternal effect on offspring immunity against hepatitis B virus - Hepatitis B virus (HBV) can cause severe liver diseases including cirrhosis and hepatocellular carcinoma (HCC). There are approximately 250 million people in the world that are chronically infected by this virus, resulting in 0.5-1 million deaths every year. Most chronic HBV carriers acquired the virus early in life from their infected mothers. In contrast to the mother-to-child transmission (i.e., vertical transmission), patients who acquired HBV from unrelated inviduals (i.e., horizontal transmission) will usually develop self-limited acute infection. Why vertical transmission leads to chronic infection whereas horizontal transmission leads to self- limited acute infection was unclear. Our recent studies indicated that HBV in the mothers could suppress anti- HBV immunity in her children to promote HBV persistence in the latter. HBV has a very narrow host range, which has greatly hampered its research. We have recently developed a mouse model to study the maternal effect on HBV persistence in her offspring. By crossing female hemizygous HBV transgenic mice to male naïve mice, we obtained non-transgenic mouse pups. When these non-transgenic mouse pups were injected with the HBV genomic DNA by hydrodynamic injection, the HBV replication persisted in the mouse liver for up to 28 weeks. This is in contrast to control mice born to non-transgenic mothers, which cleared HBV after 3-4 weeks of HBV DNA injection. Our further studies indicated that maternal HBV could condition hepatic macrophages of the offspring, which would undergo M2 polarization to suppress HBV-specific CD8+ T cells after the introduction of HBV into the mouse liver. The goal of this application is to continue our previous studies to further understand the maternal effect on offspring immunity against HBV. Specifically, we will determine how HBV in the mother impacts HBV-specific CD8+ T cells and hepatic macrophages of the offspring. We will also determine whether and how maternal HBV affects the myeloid-derived suppressor cells (MDSCs) of the offspring and the possible roles of MDSCs in the suppression of anti-HBV immunity in the offspring. Finally, we will investigate the possible effect of gut microbiota and their metabolites, specifically butyric acid, on HBV replication and anti-HBV immunity of the offspring. The proposed studies will provide important information for us to understand the mechanism of HBV persistence after its mother-to-child transmission and facilitate the development of novel therapeutic options for chronic HBV patients.


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: 2023 ( Subtotal = $641,683 )
2023	2023	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST	LOS ANGELES	CA	90089	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	5	6/26/2023	NON-COMPETING CONTINUATION	$641,683
														Subtotal = $641,683

Issue Date FY: 2022 ( Subtotal = $641,683 )
2022	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	4	6/23/2022	NON-COMPETING CONTINUATION	$641,683
														Subtotal = $641,683

Issue Date FY: 2021 ( Subtotal = $641,683 )
2021	2021	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	3	6/25/2021	NON-COMPETING CONTINUATION	$641,683
														Subtotal = $641,683

Issue Date FY: 2020 ( Subtotal = $641,683 )
2020	2020	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	2	7/2/2020	NON-COMPETING CONTINUATION	$641,683
														Subtotal = $641,683

Issue Date FY: 2019 ( Subtotal = $641,683 )
2019	2019	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	1	7/2/2019	NEW	$641,683
														Subtotal = $641,683

Grand Total All Awards = $3,208,415

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Maternal effect on offspring immunity against hepatitis B virus

Award Number: R01AI145813

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: 07/03/2019

PERIOD OF PERFORMANCE END DATE: 06/30/2024

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