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Identifying inter-kingdom microbial determinants of altered immunity in HIV exposed infants

Award Number: R00HD106861
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/12/2024
PERIOD OF PERFORMANCE END DATE: 07/31/2027

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Identifying inter-kingdom microbial determinants of altered immunity in HIV exposed infants - PROJECT ABSTRACT Infants born to HIV-infected mothers are at high risk for HIV acquisition. Additionally, HIV-exposed yet uninfected infants display reduced vaccine responses and increased disease susceptibility compared to unexposed infants. The development of certain T cell subsets, both in the mucosa and systemically, is determined by the presence of specific microbes in the gut and may be important in determining adaptive immunity. However, the gut microbiota of HIV-exposed uninfected (iHEU) infants differs from that of HIV- unexposed (iHU) infants, since their mothers have altered gut microbiota. The gut virome also plays a central role in modulating both the bacterial microbiota and immune response of adults, yet the association between the infant enteric virome and cellular responses to vaccination has not yet been explored. This study proposes that the enteric virome is one of the factors influencing the morbidity of HIV-exposed infants, either by directly altering mucosal immunity or by altering the composition of enteric bacterial communities, as a consequence of bacteriophage or other viral dynamics. This proposal will utilize an already funded, ongoing cohort to longitudinally identify interactions between viruses, bacterial microbiota, and cellular responses to vaccination in 40 iHEU and 40 iHU (Aim 1). Viral metagenome data will be integrated with bacterial community datasets and T cell cytokine responses to BCG vaccination to identify viral and bacterial taxa correlated with BCG responses. The effect of the expanded virome on bacterial microbiota and responses to BCG vaccination will then be assessed for causality in gnotobiotic mouse models (Aim 2). The effect of the expanded iHEU viroem on mucosa and peripheral gene expression will be assayed using single cell RNA sequencing in Aim 3. Integrative analyses will be used to identify interactions between specific bacterial and viral taxa, as well as their associated with BCG responses. Together, these Aims will identify mechanisms of gut dysbiosis in iHEU and reveal potential therapeutics to restore health to this group. Collectively, this proposal will reveal how maternal HIV infection shapes the enteric microbiome and immunity of associated infants.


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 = $243,522 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Child Health and Human Development Extramural Research	001	4	7/5/2025	NON-COMPETING CONTINUATION	$243,522
2025	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Child Health and Human Development Extramural Research	000	3	11/27/2024	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $243,522

Issue Date FY: 2024 ( Subtotal = $249,000 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Child Health and Human Development Extramural Research	001	3	9/18/2024	EXTENSION WITH OR WITHOUT FUNDS	$0
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Child Health and Human Development Extramural Research	000	3	9/12/2024	EXTENSION WITH OR WITHOUT FUNDS	$249,000
														Subtotal = $249,000

Grand Total All Awards = $492,522

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Identifying inter-kingdom microbial determinants of altered immunity in HIV exposed infants

Award Number: R00HD106861

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/12/2024

PERIOD OF PERFORMANCE END DATE: 07/31/2027

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