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O-Specific Polysaccharide Responses and Cholera

Award Number: R37AI106878
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: 04/01/2026
PERIOD OF PERFORMANCE END DATE: 03/31/2030

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O-Specific Polysaccharide Responses and Cholera - Cholera is a severe dehydrating illness of humans. It is endemic in over 50 countries and causes 3 to 5 million cases a year, resulting in approximately 100,000 deaths. Currently available cholera vaccines are poorly immunogenic in children under the age of 5 years, and often do not induce robust long-term memory responses in immunologically naïve populations. Antibodies targeting O-specific polysaccharide (OSP) are associated with protection against cholera. We here propose to extend our highly productive ongoing R37 international program that is defining OSP-specific immune responses in humans with cholera, including how OSP-specific antibodies protect. Such knowledge would be high impact and would directly inform cholera control efforts, including advancement of next generation cholera vaccines. In Aim #1, we will continue to define mechanisms of protection against V. cholerae afforded by OSP-specific responses using human isogenic OSP-specific monoclonal antibodies and human enteroid models. In Aim #2, we will define single cell and population responses at the mucosal surface in mucosal tissue samples obtained through endoscopic biopsy of cholera patients using single-nuclei sequencing (snRNA-seq) with T cell receptor (TCR) and B cell receptor (BCR) sequencing. In Aim #3, we will (a) define the OSP-specific response in intestinal tissue and luminal contents of patients recovering from cholera in Bangladesh, (b) deeply interrogate peripheral blood antigen-specific and functional immune responses using a system serology- based approach, and correlate these responses to responses directly assessed at the mucosal surface [in (3a)], and (c) assess the validity of whether such peripheral markers predict protection against cholera in our ongoing household contact study in Bangladesh. This extension builds upon our fully-approved and ongoing human, animal and bench-top studies, protocols and samplings, including at the International Centre for Diarrhoeal Disease Research-Bangladesh (icddr.b); no new additions are proposed. RELEVANCE (See instructions): Currently available oral cholera vaccines have a number of shortcomings. Developing improved vaccines or vaccination strategies is hampered by the reality that we do not currently understand the mechanism of immune protection against cholera although it is known that a primary component of that immunity targets O-specific polysaccharide (OSP) of V. cholerae. We here propose an investigative approach to define and evaluate OSP-specific responses during cholera.


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: 2026 ( Subtotal = $756,792 )
2026	2026	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	12	4/27/2026	SUPPLEMENT FOR EXPANSION	$123,400
2026	2026	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	12	4/13/2026	NON-COMPETING CONTINUATION	$633,392
														Subtotal = $756,792

Issue Date FY: 2025 ( Subtotal = $799,285 )
2025	2025	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	11	1/14/2025	EXTENSION WITH OR WITHOUT FUNDS	$799,285
2025	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	10	8/1/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $799,285

Issue Date FY: 2024 ( Subtotal = $739,887 )
2024	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	10	2/22/2024	NON-COMPETING CONTINUATION	$665,899
2024	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	10	5/24/2024	NON-COMPETING CONTINUATION	$73,988
														Subtotal = $739,887

Issue Date FY: 2023 ( Subtotal = $739,887 )
2023	2023	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	9	3/2/2023	NON-COMPETING CONTINUATION	$739,887
														Subtotal = $739,887

Issue Date FY: 2022 ( Subtotal = $739,487 )
2022	2022	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	8	3/29/2022	NON-COMPETING CONTINUATION	$739,487
														Subtotal = $739,487

Issue Date FY: 2021 ( Subtotal = $850,350 )
2021	2021	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Allergy and Infectious Diseases Research	003	7	6/17/2021	NON-COMPETING CONTINUATION	$0
2021	2021	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	7	3/15/2021	NON-COMPETING CONTINUATION	$739,487
2021	2020	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Allergy and Infectious Diseases Research	002	6	6/17/2021	COMPETING CONTINUATION	$0
2021	2020	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	6	3/22/2021	COMPETING CONTINUATION	$110,863
														Subtotal = $850,350

Grand Total All Awards = $4,625,688

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O-Specific Polysaccharide Responses and Cholera

Award Number: R37AI106878

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: 04/01/2026

PERIOD OF PERFORMANCE END DATE: 03/31/2030

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