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Phage Resistance in Emergent Vibrio cholerae and Phage Prophylaxis of Cholera

Award Number: R37AI055058
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: 05/15/2003
PERIOD OF PERFORMANCE END DATE: 01/31/2030

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Phage Resistance in Emergent Vibrio cholerae and Phage Prophylaxis of Cholera - PROJECT SUMMARY (See instructions): Bacteriophages (phages) are viruses that specifically kill bacteria but are safe for humans. Phages have been shown to play important roles in the life cycle of many bacterial pathogens, particularly water-borne pathogens that cause gastrointestinal tract infections. For example, the temperate phages, which integrate their DNA into the bacterial genome, often increase the fitness of their host by providing virulence factors such as toxins. Other phages, known as lytic or virulent phages, can play negative roles by infecting and killing their host bacterium, thus reducing the number of pathogen below the threshold needed to cause disease. Vibrio cholerae is a water-borne pathogen that infects the small intestine to cause the severe diarrheal disease cholera. Our published and preliminary data indicate a pervasive negative role for several virulent phages commonly found in cholera-endemic areas around the Bay of Bengal. These virulent phages reduce the virulence, transmission, and dissemination of V. cholerae. Sensitivity to most of these phages, particularly to phage ICP3, has been consistent among clinical isolates collected over the past 20 years, opening up the possibility of using a cocktail of phages for preventing cholera in people at high risk, such as household contacts of cholera index patients. However, in 2022, a new multidrug-, multiphage-resistant strain emerged in Bangladesh that threatens the prevention and treatment of cholera. ICP3 alone retains the ability to kill this newly emerged strain. In this project, we will investigate the potential of ICP3 as a single phage product for preventing cholera. We will determine if there is a mucosal immune response to orally administered ICP3 and whether it is neutralizing. In addition, we will identify and characterize phage resistance mechanisms in emergent strains of V. cholerae.


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 = $519,048 )
2025	2025	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	002	21	5/12/2025	EXTENSION WITH OR WITHOUT FUNDS	$73,726
2025	2025	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	21	1/23/2025	EXTENSION WITH OR WITHOUT FUNDS	$519,048
2025	2024	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	20	5/12/2025	NON-COMPETING CONTINUATION	-$73,726
														Subtotal = $519,048

Issue Date FY: 2024 ( Subtotal = $465,324 )
2024	2024	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	20	2/1/2024	NON-COMPETING CONTINUATION	$418,792
2024	2024	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	20	5/23/2024	NON-COMPETING CONTINUATION	$46,532
														Subtotal = $465,324

Issue Date FY: 2023 ( Subtotal = $464,976 )
2023	2023	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	19	2/9/2023	NON-COMPETING CONTINUATION	$464,976
														Subtotal = $464,976

Issue Date FY: 2022 ( Subtotal = $464,978 )
2022	2022	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	18	1/7/2022	NON-COMPETING CONTINUATION	$464,560
2022	2020	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	16	7/11/2022	COMPETING CONTINUATION	$418
														Subtotal = $464,978

Issue Date FY: 2021 ( Subtotal = $504,161 )
2021	2021	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	17	1/14/2021	NON-COMPETING CONTINUATION	$462,612
2021	2020	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	16	12/11/2020	COMPETING CONTINUATION	$41,549
														Subtotal = $504,161

Issue Date FY: 2020 ( Subtotal = $478,061 )
2020	2020	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	16	7/31/2020	COMPETING CONTINUATION	$0
2020	2020	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	16	12/4/2019	COMPETING CONTINUATION	$478,061
														Subtotal = $478,061

Grand Total All Awards = $2,896,547

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Phage Resistance in Emergent Vibrio cholerae and Phage Prophylaxis of Cholera

Award Number: R37AI055058

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: 05/15/2003

PERIOD OF PERFORMANCE END DATE: 01/31/2030

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