Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

A systems immunology approach to evaluate malaria vaccine performance in endemic regions of Kenya

Award Number: U01AI165524
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: 02/01/2022
PERIOD OF PERFORMANCE END DATE: 01/31/2027

Group Awards By:

View Award Description

A systems immunology approach to evaluate malaria vaccine performance in endemic regions of Kenya - A highly effective malaria vaccine remains the ultimate tool for malaria control and elimination. The front runner is RTS,S/AS01, a recombinant protein comprising portions of Plasmodium falciparum (Pf) circumsporozoite protein (CSP). However, the observed vaccine efficacy to clinical malaria in children living in malaria endemic settings is only 36%. In order to understand how to improve upon this vaccine, a comprehensive evaluation of baseline and cumulative factors that impede malaria vaccine performance, in direct contrast to factors associated with protection from malaria, is needed. We have recently defined stronger correlates of protection based on functional antibody activity using a systems serology approach. To date, these system serology studies have been conducted only for adults from non-endemic regions. Here, we aim to test the overall hypothesis that children living in malaria endemic areas who have less mature or aberrant immune cells are unable to develop the breadth of functional antibodies and T cells elicited by RTS,S in order to become protected against malaria. Drawing on the WHO Malaria Vaccine Implementation Program in a high- transmission region in Kenya, we will employ an intensive longitudinal cohort study design to follow children during their 4-dose RTS,S vaccination schedule, with active and passive follow-up for Pf infections and episodes of clinical malaria until they reach 4 years of age. Our overall hypothesis will be tested by the following specific aims: SA1: To comprehensively characterize baseline and peri-vaccination factors that correlate with vaccine hyporesponsiveness. Using an integrated systems immunology and machine learning approach, we will determine the effects of ongoing exposures to malaria, systemic inflammation, pre- existing anti-malarial immunity, and immaturity of cellular immune signatures on RTS,S vaccine hypo- responsiveness, defined as the inability to develop a core group of functional anti-CSP antibodies. SA2: To comprehensively characterize the post-vaccination immune signatures in children that correlate with protection from malaria. Using a systems immunology approach, we will determine the function of vaccine- elicited anti-CSP antibodies and their correlation with age, cellular immune signatures, and protection from malaria. Functional in vitro studies will assess antibody opsonization of sporozoites and antibody-dependent cellular cytotoxicity with and without innate immune cells; assess the phenotype and function of vaccine- elicited CSP-specific T cells; and explore the potential for epigenetic modifications of monocytes (trained immunity) to influence vaccine performance. Using a computational modeling/machine learning approach, we will integrate deep immunoprofiling features to predict correlates with protection from malaria. Together, this study aims to inform the next generation of malaria vaccines and vaccination programs that could include immune-modulatory components or recommendations to combine antimalarial prophylaxis/treatment within the vaccine schedule.


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 = $987,656 )
2026	2026	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Allergy and Infectious Diseases Research	001	5	2/18/2026	SUPPLEMENT FOR EXPANSION	$96,682
2026	2026	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Allergy and Infectious Diseases Research	000	5	1/30/2026	NON-COMPETING CONTINUATION	$890,974
														Subtotal = $987,656

Issue Date FY: 2025 ( Subtotal = $958,026 )
2025	2025	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Allergy and Infectious Diseases Research	000	4	2/13/2025	NON-COMPETING CONTINUATION	$958,026
														Subtotal = $958,026

Issue Date FY: 2024 ( Subtotal = $987,656 )
2024	2024	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Allergy and Infectious Diseases Research	000	3	1/26/2024	NON-COMPETING CONTINUATION	$888,892
2024	2024	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Allergy and Infectious Diseases Research	001	3	5/23/2024	NON-COMPETING CONTINUATION	$98,764
														Subtotal = $987,656

Issue Date FY: 2023 ( Subtotal = $987,659 )
2023	2023	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Allergy and Infectious Diseases Research	000	2	2/1/2023	NON-COMPETING CONTINUATION	$987,659
2023	2023	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Allergy and Infectious Diseases Research	001	2	6/23/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $987,659

Issue Date FY: 2022 ( Subtotal = $987,659 )
2022	2022	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Allergy and Infectious Diseases Research	000	1	1/27/2022	NEW	$987,659
														Subtotal = $987,659

Grand Total All Awards = $4,908,656

Top

All Categories

About

Search

Reports

Data Submission

Award Information

A systems immunology approach to evaluate malaria vaccine performance in endemic regions of Kenya

Award Number: U01AI165524

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: 02/01/2022

PERIOD OF PERFORMANCE END DATE: 01/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer