Friday, October 31, 2025 10/31/2025

Malaria variant surface antigen expression and vulnerability to disease in Malian children with Hemoglobin C trait

Award Number: R01HL146377
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2019
PERIOD OF PERFORMANCE END DATE: 06/30/2024

Group Awards By:

View Award Description

Malaria variant surface antigen expression and vulnerability to disease in Malian children with Hemoglobin C trait - PROJECT SUMMARY In 2015, malaria killed 292,000 children under five years of age in sub-Saharan Africa. Hemoglobinopathies provide protection against malarial disease and reflect the powerful selective force of malaria on the human genome. In rural Mali, hemoglobin C trait provides protection against severe malaria and uncomplicated malaria illness. The precise mechanisms that protect children with hemoglobin C trait against malaria illness is unclear, but appear to be linked to Plasmodium falciparum malaria parasite variant antigens on the surface of infected erythrocytes that play a critical role in mediating disease severity. These variant surface antigens bind to host receptors in the endothelial membrane, facilitating tissue sequestration and avoidance of splenic clearance. The natural acquisition of immunity to P. falciparum malaria in infants and young children likely depends on the development of protective antibody responses against these variant surface antigens. Hemoglobin C trait decreases the quantity of these antigens on the surface of infected erythrocytes and alters their display. We have found that Malian children with hemoglobin C trait have reduced serorecognition of variant surface antigens compared to wild type children, suggesting that abnormally expressed variant surface antigens limit the antibody response. We hypothesize that a primary protective mechanism against malaria in children with Hemoglobin C trait is abnormal expression of a subset of parasite variant surface antigens. Identifying these abnormally expressed variant surface antigens may yield a subset of malaria proteins critical to disease pathogenesis. Using novel transcriptomic and proteogenomic techniques, we aim to identify the transcripts (Aim 1) and expressed variant surface antigens (Aim 2) in infections in children with hemoglobin AC, AA, and AS in a recent longitudinal study of malaria incidence in rural Mali. We will identify transcription and expression differences in variant surface antigens between these groups with respect to clinical and asymptomatic malaria episodes. We will then measure how seroreactivity changes to these variant surface antigens following a symptomatic versus an asymptomatic infection in these groups (Aim 3) with a custom protein microarray so that we can link disease vulnerability with variant surface antigen expression. The contributions of our research will be to identify variant surface antigen transcripts in symptomatic and asymptomatic infections of Malian children with hemoglobin AC, AA, and AS; variant surface antigens present on the surface of infected erythrocytes in these infections; and differences in seroreactivity to variant surface antigens. Our approach will determine if the effects of hemoglobin C trait occur during transcription or protein expression and translocation to the erythrocyte surface. Our ultimate goal is to identify a subset of variant surface antigen epitopes for a malaria vaccine to protect against clinical disease. Upon completion, we will be prepared to precisely map and define epitopes underlying natural protection to clinical malaria for the variant surface antigens identified as critical to disease pathogenesis and hemoglobin C trait protection.


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: 2023 ( Subtotal = $454,076 )
2023	2023	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Blood Diseases and Resources Research	002	5	8/2/2023	NON-COMPETING CONTINUATION	$0
2023	2023	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Blood Diseases and Resources Research	000	5	7/11/2023	NON-COMPETING CONTINUATION	$340,407
2023	2023	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Blood Diseases and Resources Research	001	5	7/14/2023	SUPPLEMENT FOR EXPANSION	$113,669
														Subtotal = $454,076

Issue Date FY: 2022 ( Subtotal = $347,585 )
2022	2022	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Blood Diseases and Resources Research	000	4	6/10/2022	NON-COMPETING CONTINUATION	$347,585
														Subtotal = $347,585

Issue Date FY: 2021 ( Subtotal = $354,605 )
2021	2021	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Blood Diseases and Resources Research	000	3	6/7/2021	NON-COMPETING CONTINUATION	$354,605
														Subtotal = $354,605

Issue Date FY: 2020 ( Subtotal = $362,548 )
2020	2020	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Blood Diseases and Resources Research	000	2	6/24/2020	NON-COMPETING CONTINUATION	$362,548
														Subtotal = $362,548

Issue Date FY: 2019 ( Subtotal = $370,799 )
2019	2019	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Blood Diseases and Resources Research	000	1	6/24/2019	NEW	$370,799
														Subtotal = $370,799

Grand Total All Awards = $1,889,613

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Malaria variant surface antigen expression and vulnerability to disease in Malian children with Hemoglobin C trait

Award Number: R01HL146377

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2019

PERIOD OF PERFORMANCE END DATE: 06/30/2024

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer