Monday, December 15, 2025 12/15/2025

Protective immunity following dengue virus natural infections and vaccination

Award Number: P01AI106695
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: 07/29/2015
PERIOD OF PERFORMANCE END DATE: 07/31/2030

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Protective immunity following dengue virus natural infections and vaccination - SUMMARY (OVERALL) The four dengue virus serotypes (DENV1-4) cause the most important mosquito-borne viral disease of humans. Yet, no treatment is available, and the only registered vaccines are problematic. A major challenge is the dual potential of the immune response to protect against or enhance future infection with a different DENV serotype. Thus, it is critical to better understand immune responses to natural DENV infections and vaccines and to identify robust correlates of protection. The overall goal of this P01 is to apply state-of-the-art immunological and virological methods in the context of clinical and epidemiological studies of DENV infections and vaccines to elucidate how adaptive immunity shapes clinical and immunological outcomes. Our current P01 has been very successful, generating ~80 high-level publications since its inception and ~30 publications in the last 3.5 years, producing key findings that are timely and impactful. Further, our P01 consortium has served as a go-to resource for multiple agencies and regulatory bodies regarding dengue medical countermeasures. Here, we build on new tools and hypotheses that emerged from our current P01 to study immunological imprinting and evaluate biomarkers of protection and risk. The overall hypothesis of this P01 is that the magnitude and quality (i.e., repertoire and functionality) of DENV antibody (Ab), B cell, and T cell responses are shaped by distinct structural and antigenic characteristics of the 4 serotypes both in primary (1°) infections and, via immunological imprinting, secondary (2°) infections -- impacting clinical and epidemiological outcomes, with important implications for vaccine design and efficacy. We propose a coordinated P01 with 3 projects: 1) Immunological imprinting and immune correlates of Ab and B cell responses in natural DENV infections; 2) Linkage of vaccine-induced human B cell and Ab response to protective or dengue disease-enhancing immunity; and 3) Immunological imprinting of T cell responses following DENV natural infection and vaccination, supported by 4 cores: 1) Administrative; 2) Viral Assays; 3) Clinical, Data Management, and Statistical Modeling, and 4) Antibodyomics. We leverage unique sample sets from the longest continuous cohort study of dengue (in Nicaragua), currently in its 20th year; a placebo-controlled cohort study of the Dengvaxia® vaccine in the Philippines; and a human vaccine challenge study of a monovalent NIH vaccine. The P01 is highly synergistic in that samples are shared and infection sequences aligned among Projects and Cores. Specific Aims are: 1) Determine how DENV1-4 B cell and Ab responses are shaped by distinct structural and antigenic characteristics in 1° and, via immunological imprinting, in 2° infections; 2) Reveal Ab-mediated mechanisms responsible for vaccine-mediated protection, vaccine failure and vaccine-enhanced dengue disease; 3) Profile the quantity and quality of imprinted DENV-specific memory T cell response in relation to immunophenotype and vaccine outcomes; 4) Compare the breadth of Ab and T cell responses induced by DENV vaccines vs. natural infections; 5) Identify robust correlates of protection or risk enhancement of dengue disease in different contexts.


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 = $3,121,080 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Allergy and Infectious Diseases Research	001	11	9/12/2025	COMPETING CONTINUATION	$3,121,080
2025	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Allergy and Infectious Diseases Research	000	10	9/12/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $3,121,080

Issue Date FY: 2024 ( Subtotal = $2,527,162 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Allergy and Infectious Diseases Research	000	10	8/2/2024	NON-COMPETING CONTINUATION	$2,527,162
														Subtotal = $2,527,162

Issue Date FY: 2023 ( Subtotal = $2,527,162 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Allergy and Infectious Diseases Research	000	9	8/1/2023	NON-COMPETING CONTINUATION	$2,527,162
														Subtotal = $2,527,162

Issue Date FY: 2022 ( Subtotal = $2,624,793 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Allergy and Infectious Diseases Research	000	8	8/25/2022	NON-COMPETING CONTINUATION	$2,539,162
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Allergy and Infectious Diseases Research	001	8	9/16/2022	SUPPLEMENT FOR EXPANSION	$85,631
														Subtotal = $2,624,793

Issue Date FY: 2021 ( Subtotal = $2,629,744 )
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 220	BERKELEY	CA	94710	ALAMEDA	USA	Allergy and Infectious Diseases Research	003	7	8/26/2021	SUPPLEMENT FOR EXPANSION	$85,631
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 220	BERKELEY	CA	94710	ALAMEDA	USA	Allergy and Infectious Diseases Research	002	7	7/28/2021	NON-COMPETING CONTINUATION	$2,544,113
2021	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Allergy and Infectious Diseases Research	001	6	3/23/2021	COMPETING CONTINUATION	$574,059
2021	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Allergy and Infectious Diseases Research	000	5	3/23/2021	NON-COMPETING CONTINUATION	-$574,059
														Subtotal = $2,629,744

Issue Date FY: 2020 ( Subtotal = $2,579,906 )
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 220	BERKELEY	CA	94710	ALAMEDA	USA	Allergy and Infectious Diseases Research	000	6	8/21/2020	COMPETING CONTINUATION	$2,579,906
														Subtotal = $2,579,906

Issue Date FY: 2019 ( Subtotal = $2,082,273 )
2019	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 220	BERKELEY	CA	94710	ALAMEDA	USA	Allergy and Infectious Diseases Research	000	5	7/10/2019	NON-COMPETING CONTINUATION	$2,082,273
														Subtotal = $2,082,273

Issue Date FY: 2018 ( Subtotal = $2,160,531 )
2018	2018	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	2150 SHATTUCK AVE RM 313	BERKELEY	CA	94704	ALAMEDA	USA	Allergy and Infectious Diseases Research	001	4	7/6/2018	NON-COMPETING CONTINUATION	$2,125,099
2018	2018	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	2150 SHATTUCK AVE RM 313	BERKELEY	CA	94704	ALAMEDA	USA	Allergy and Infectious Diseases Research	000	3	1/24/2018	SUPPLEMENT FOR EXPANSION	$35,432
														Subtotal = $2,160,531

Issue Date FY: 2017 ( Subtotal = $2,857,784 )
2017	2017	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	2150 SHATTUCK AVE RM 313	BERKELEY	CA	94704	ALAMEDA	USA	Allergy and Infectious Diseases Research	001	2	7/6/2017	SUPPLEMENT FOR EXPANSION	$0
2017	2017	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	2150 SHATTUCK AVE RM 313	BERKELEY	CA	94704	ALAMEDA	USA	Allergy and Infectious Diseases Research	002	3	7/12/2017	NON-COMPETING CONTINUATION	$2,755,298
2017	2017	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	2150 SHATTUCK AVE RM 313	BERKELEY	CA	94704	ALAMEDA	USA	Allergy and Infectious Diseases Research	000	2	5/17/2017	SUPPLEMENT FOR EXPANSION	$102,486
														Subtotal = $2,857,784

Issue Date FY: 2016 ( Subtotal = $2,996,634 )
2016	2016	UNIVERSITY OF CALIFORNIA, REGENTS	481 UNIVERSITY HALL	BERKELEY	CA	94704	ALAMEDA	USA	Allergy and Infectious Diseases Research	000	2	6/20/2016	NON-COMPETING CONTINUATION	$2,080,082
2016	2016	UNIVERSITY OF CALIFORNIA, REGENTS	481 UNIVERSITY HALL	BERKELEY	CA	94704	ALAMEDA	USA	Allergy and Infectious Diseases Research	002	2	8/17/2016	NON-COMPETING CONTINUATION	$149,992
2016	2016	UNIVERSITY OF CALIFORNIA, REGENTS	481 UNIVERSITY HALL	BERKELEY	CA	94704	ALAMEDA	USA	Allergy and Infectious Diseases Research	001	2	8/4/2016	NON-COMPETING CONTINUATION	$766,560
														Subtotal = $2,996,634

Issue Date FY: 2015 ( Subtotal = $2,106,690 )
2015	2015	UNIVERSITY OF CALIFORNIA, REGENTS	481 UNIVERSITY HALL	BERKELEY	CA	94704	ALAMEDA	USA	Allergy and Infectious Diseases Research	000	1	7/29/2015	NEW	$2,106,690
														Subtotal = $2,106,690

Grand Total All Awards = $28,213,759

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Protective immunity following dengue virus natural infections and vaccination

Award Number: P01AI106695

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: 07/29/2015

PERIOD OF PERFORMANCE END DATE: 07/31/2030

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