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Interpersonal variation in microbiome structure modulates inter-individual immune responses to Vibrio cholerae

Award Number: F31AI179030
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 12/26/2023
PERIOD OF PERFORMANCE END DATE: 12/25/2026

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Interpersonal variation in microbiome structure modulates inter-individual immune responses to Vibrio cholerae - PROJECT SUMMARY Vibrio cholerae is a Gram-negative bacterium and the etiologic agent of cholera, a severe human diarrheal disease characterized by voluminous watery diarrhea and vomiting and when left untreated, severe dehydration, hypovolemic shock, and death. Several oral cholera vaccines (OCV) have been developed but demonstrate variable efficacy in distinct geographical regions. Thus, defining the factors that modulate such variation and developing strategies to minimize variability in prophylactic efficacy remains a significant global health priority. One host-associated factor that has demonstrated differences in composition and functional output between populations of high and low OCV efficacy is the commensal microbial community of the gastrointestinal tract, the gut microbiota. Our central hypothesis is that interpersonal variation in the microbial community of the gastrointestinal tract contributes to significant interpersonal variation in OCV responses caused by microbe-specific modulation of the intestinal immune system. Our preliminary data suggest that the gut microbiota may acts a personalized contributor to oral cholera vaccination outcome, whereby (i) specific microbial taxa correlate with distinct immune responses to oral cholera vaccination; (ii), inter-individual variation in microbiota structure and (iii) dysbiotic microbiotas, representative of gut microbial communities found in cholera endemic areas, directly influence infection and vaccination outcomes to V. cholerae; and (iv) modulation of host intestinal CD4+ T-cells regulate host immune responses to V. cholerae challenge. Precision editing of the gut microbiota may represent an effective strategy to enhance oral vaccine responsiveness, but such approaches will require a detailed understanding of the specific microbe(s) involved and the particular mechanisms by which they enhance or inhibit human immunophenotypes of interest, particularly in the context of oral vaccine responses. Our ultimate goal is to identify specific microbial taxa that drive differential immune responses to V. cholerae, as such candidates may better inform the development of gut microbiota-targeted prebiotic and probiotic strategies for cholerae prophylaxis. We will address this problem with the following study aims: Aim 1 - Determine the effect of inter- individual microbiota variation on OCV responsiveness; Aim 2 - Define immune cell populations that mediate microbiota-driven effects on OCV responses.


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 = $42,034 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Allergy and Infectious Diseases Research	000	2	12/20/2024	NON-COMPETING CONTINUATION	$32,974
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Allergy and Infectious Diseases Research	001	2	8/8/2025	NON-COMPETING CONTINUATION	$9,060
														Subtotal = $42,034

Issue Date FY: 2023 ( Subtotal = $40,190 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Allergy and Infectious Diseases Research	001	1	6/26/2023	NEW	$0
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Allergy and Infectious Diseases Research	000	1	6/26/2023	NEW	$40,190
														Subtotal = $40,190

Grand Total All Awards = $82,224

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Interpersonal variation in microbiome structure modulates inter-individual immune responses to Vibrio cholerae

Award Number: F31AI179030

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 12/26/2023

PERIOD OF PERFORMANCE END DATE: 12/25/2026

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