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Identifying functional antibody responses that protect against malaria in children

Award Number: R01AI165595
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: 08/15/2022
PERIOD OF PERFORMANCE END DATE: 07/31/2027

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Identifying functional antibody responses that protect against malaria in children - This project aims to identify the targets and features of antibody responses that determine the outcome of malaria infection in young African children. It uses Systems Serology, combining multi-dimensional antibody profiling with machine learning, to study responses to Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), the dominant antigen on the surface of malaria infected erythrocytes (IEs). Some PfEMP1 types are implicated in cerebral malaria (CM); others may lead to asymptomatic parasitemia (AP). Asymptomatic infections contribute to ongoing malaria transmission. Understanding how the host and parasite strike this balance is important not only for malaria control and eradication efforts, but also for understanding this symbiotic relationship in other common infections (Covid-19, tuberculosis, AIDS). The proposed study is based in Blantyre, Malawi where children with CM have retinal exams and MRI scans to assess neurovascular involvement and brain swelling, respectively. In Aim 1, we use Luminex technology on acute and convalescent plasma and parasite isolates to characterize antibody response to a broad range of PfEMP1 protein fragments implicated in severe malaria, and from these we will compare children with CM (with and without retinopathy and brain swelling) and note changes that develop in convalescence. In Aim 2, priority PfEMP1s identified in Aim 1 will be studied in depth to identify the immunological mechanisms involved in each of these phenotypes. These studies will use cell-based assays of phagocytosis, respiratory burst and activation with both PfEMP1 fragments and parasite lines expressing known PfEMP1 types. Aim 3 uses community cohorts including children with AP, to study how antibodies to PfEMP1 and to merozoite antigens influence the evolution of AP, to identify antibody responses that prevent progression to clinical disease These comprehensive, integrated studies will compare and contrast antibody responses that protect against CM, against UM, and that allow AP. The scientific knowledge gained from these studies regarding AP will be applicable to other pathogens which also co-exist equably with the host. Despite being asymptomatic, these pathogens remain transmissible and can be spread to innocent bystanders, potentially causing disease. Infection with M. tuberculosis, HIV, and SARS-CoV-2, all have significant impact on the health of American citizens and all use strategies leading to latent or asymptomatic infections. The Systems Serology techniques used in this proposal will identify antibody characteristics and immunologic mechanisms that function to keep P. falciparum infection asymptomatic and may shed light the mechanisms used by other pathogens that employ the same survival technique. These studies will not only inform our understanding of malaria pathogenesis and vaccine design but will generate knowledge translatable to diseases more frequently seen in the United States, thereby improving the health of Americans.


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 = $332,239 )
2026	2026	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 360	EAST LANSING	MI	48824	INGHAM	USA	Allergy and Infectious Diseases Research	001	5	8/4/2026	SUPPLEMENT FOR EXPANSION	$158,782
2026	2026	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 360	EAST LANSING	MI	48824	INGHAM	USA	Allergy and Infectious Diseases Research	000	5	7/24/2026	NON-COMPETING CONTINUATION	$173,457
														Subtotal = $332,239

Issue Date FY: 2025 ( Subtotal = $333,753 )
2025	2025	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Allergy and Infectious Diseases Research	000	4	9/3/2025	NON-COMPETING CONTINUATION	$220,101
2025	2025	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Allergy and Infectious Diseases Research	001	4	9/5/2025	SUPPLEMENT FOR EXPANSION	$113,652
														Subtotal = $333,753

Issue Date FY: 2024 ( Subtotal = $516,591 )
2024	2024	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Allergy and Infectious Diseases Research	000	3	7/18/2024	NON-COMPETING CONTINUATION	$516,591
														Subtotal = $516,591

Issue Date FY: 2023 ( Subtotal = $529,422 )
2023	2023	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Allergy and Infectious Diseases Research	000	2	7/17/2023	NON-COMPETING CONTINUATION	$529,422
														Subtotal = $529,422

Issue Date FY: 2022 ( Subtotal = $559,136 )
2022	2022	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Allergy and Infectious Diseases Research	000	1	8/15/2022	NEW	$559,136
														Subtotal = $559,136

Grand Total All Awards = $2,271,141

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Identifying functional antibody responses that protect against malaria in children

Award Number: R01AI165595

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: 08/15/2022

PERIOD OF PERFORMANCE END DATE: 07/31/2027

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