Wednesday, March 11, 2026 3/11/2026

Correlates of protective immunity to HCV and rational vaccine design

Award Number: U19AI159819
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/15/2021
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Correlates of protective immunity to HCV and rational vaccine design - Abstract Prevention of HCV infection remains an important public health objective even with the recent adoption of highly effective antiviral therapies. Importantly, treatment with direct acting antivirals (DAAs) does not prevent reinfection in those who have successfully been treated. A vaccine to prevent HCV persistence is needed to stem an emerging epidemic of infection in adolescents and young adults who inject drugs that have limited access to screening and treatment. Only twenty five percent of acute HCV infections resolve spontaneously. Resolution does, however, sharply reduce the risk of persistent infection upon re-exposure to the virus. Memory CD4+ T helper and CD8+ cytotoxic T cell responses contribute to accelerated clearance of a second infection. However, the role of neutralizing antibodies during reinfection is less clear. Importantly, vaccines to generate an equivalent T cell response failed to thwart off the rate of persistence in naïve recipients. Here, we will test the central hypothesis that memory CD4+ T cells contribute significantly to HCV reinfection outcome by promoting expansion of HCV-specific B cells and production of broadly neutralizing antibodies that contribute to viral clearance. Unique features of this proposal are (i) the use of longitudinal samples from the Montreal cohort of high- risk people who inject drugs. Participants are monitored prior to, during, and after HCV infection and then subsequently followed again when they have been re-exposed to HCV a second time after resolving their primary infection. (ii) We have assembled a team of investigators in Cairo, Egypt who will assist us with recruiting and treating subjects undergoing DAA treatment. Egypt has the highest prevalence of HCV infection in the world. In 2014, Egypt's government has made DAA treatment affordable and 2.5 million subjects have started treatment. Understanding the immune responses in these two cohorts will provide us with valuable information to develop an efficacious vaccine regimen that would emulate the successful responses generated during a natural challenge with HCV. Three highly interactive Projects are proposed. Project 1 (N. Shoukry, PI) will compare the frequency, breadth, function, and phenotype of CD4+ T cells in HCV reinfections that either resolve or become persistent. Project 2 (A. Grakoui, PI) will use new state of the art technology to isolate and characterize antigen-specific B cells during HCV reinfection and post DAA treatment. Project 3 (R. Amara, PI) will develop vaccine modalities to induce both a CD4+ T helper response and a robust antigen-specific antibody response in blood and liver using DNA, modified vaccinia Ankara (MVA) and protein-based vaccines against HCV proteins in non-human primates.


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 = $0 )
2026	2025	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	5	12/2/2025	NON-COMPETING CONTINUATION	$0
2026	2025	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	001	5	1/28/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $1,918,702 )
2025	2025	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	001	5	9/12/2025	SUPPLEMENT FOR EXPANSION	$259,994
2025	2025	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	002	5	9/15/2025	SUPPLEMENT FOR EXPANSION	$25,083
2025	2025	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	5	9/9/2025	NON-COMPETING CONTINUATION	$1,633,625
														Subtotal = $1,918,702

Issue Date FY: 2024 ( Subtotal = $2,010,344 )
2024	2024	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	4	3/15/2024	NON-COMPETING CONTINUATION	$2,010,344
														Subtotal = $2,010,344

Issue Date FY: 2023 ( Subtotal = $2,054,221 )
2023	2023	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	001	3	9/8/2023	NON-COMPETING CONTINUATION	$0
2023	2023	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	3	5/1/2023	NON-COMPETING CONTINUATION	$2,054,221
														Subtotal = $2,054,221

Issue Date FY: 2022 ( Subtotal = $2,040,307 )
2022	2022	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	2	4/11/2022	NON-COMPETING CONTINUATION	$2,040,307
														Subtotal = $2,040,307

Issue Date FY: 2021 ( Subtotal = $2,018,828 )
2021	2021	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	1	4/15/2021	NEW	$2,018,828
														Subtotal = $2,018,828

Grand Total All Awards = $10,042,402

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Correlates of protective immunity to HCV and rational vaccine design

Award Number: U19AI159819

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 04/15/2021

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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