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Intestinal microbiota-mediated rotavirus vaccine failure

Award Number: R01AI170014
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: 09/19/2022
PERIOD OF PERFORMANCE END DATE: 07/31/2027

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Intestinal microbiota-mediated rotavirus vaccine failure - PROJECT SUMMARY Infection of gut epithelia by attenuated rotavirus (RV) vaccines serves to protect millions of lives annually. It is increasingly appreciated that gut microbiota, which shape the milieu in which rotaviruses encounter the epithelium is a pivotal determinant of rotavirus vaccine efficacy. Indeed, RV vaccines have proven to be much less effective in developing countries which are known to have stark differences in gut microbiota composition. Our published work demonstrates that microbiota can both directly impact RV and, moreover, impact gut epithelia to prevent against its entry and replication. Furthermore, our unpublished work compellingly argues for a central role for gut microbiota composition in RV vaccine inefficacy. Specifically, we find that transplant of microbiota from non-RV vaccine responding children confers a microbiota-dependent non-responder phenotype. In addition, culturing infant fecal samples in bioreactor continuous culture systems yields supernatants that differentially inhibit RV vaccine replication in vitro. Hence, the central goals of this proposal are to identify and isolate microbiota constituents that drive RV vaccine inefficacy in humans and determine mechanisms by which they act. Findings from this work will advance our fundamental knowledge on bacterial-viral interactions in the gut, mechanistically enlighten how microbiota can impact replication and response to live, attenuated oral vaccines and potentially aid in the development of novel strategies to reduce the burden of enteric viral infections.


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: 2024 ( Subtotal = $783,735 )
2024	2024	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION INC	58 EDGEWOOD AVE NE	ATLANTA	GA	30303	FULTON	USA	Allergy and Infectious Diseases Research	000	3	7/24/2024	NON-COMPETING CONTINUATION	$783,735
														Subtotal = $783,735

Issue Date FY: 2023 ( Subtotal = $783,735 )
2023	2023	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION INC	58 EDGEWOOD AVE NE	ATLANTA	GA	30303	FULTON	USA	Allergy and Infectious Diseases Research	000	2	7/21/2023	NON-COMPETING CONTINUATION	$783,735
														Subtotal = $783,735

Issue Date FY: 2022 ( Subtotal = $772,481 )
2022	2022	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC.	58 EDGEWOOD AVE NE 3RD FL	ATLANTA	GA	30303	FULTON	USA	Allergy and Infectious Diseases Research	000	1	9/19/2022	NEW	$772,481
														Subtotal = $772,481

Grand Total All Awards = $2,339,951

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Intestinal microbiota-mediated rotavirus vaccine failure

Award Number: R01AI170014

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: 09/19/2022

PERIOD OF PERFORMANCE END DATE: 07/31/2027

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