# Identifying functional antibody responses that protect against malaria in children

> **NIH NIH R01** · MICHIGAN STATE UNIVERSITY · 2024 · $516,591

## Abstract

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). We also study key merozoite antigens,
which are implicated in protection from asymptomatic parasitemia (AP) or uncomplicated malaria (UM).
Responses include antibody subclass, isotype, and Fc receptor and complement engagement, together with
antibody glycosylation and avidity. Some PfEMP1 types are implicated in cerebral malaria (CM); others may
influence outcomes across a spectrum which includes AP, clearance of parasites and progression to UM. Our
earlier work validates this approach. We applied Systems Serology to pregnancy malaria and were able to
identify seven key responses to the PfEMP1 that mediates placental malaria (VAR2CSA), that distinguished
women susceptible to placental malaria from protected women. Four of these seven were IE based assays.
The proposed study is based in Blantyre, Malawi, an International Center of Excellence in Malaria Research
(ICEMR) site. In ongoing studies, children with CM have retinal exams and MRI scans to assess neurovascular
involvement and brain swelling, respectively. Cohorts of controls with UM and community controls with AP are
enrolled and sustained. 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. From these analyses we will identify antibody responses to PfEMP1 domains that are lacking in children
with CM, that differ between children with or without retinopathy and brain swelling, and that develop in
convalescence from CM.
In Aim 2, priority PfEMP1s identified in Aim 1 are studied in depth using cell-based assays of phagocytosis,
respiratory burst and activation with both PfEMP1 fragments and parasite lines expressing similar PfEMP1 types.
We have established assays using monocytes, neutrophils, NK cells and whole blood for this purpose.
Aim 3 uses community cohorts recruited by the Malawi ICEMR, 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 UM or lead to clearance of infection. These comprehensive, integrated studies will
compare and contrast antibody responses that protect against CM, against UM, and that clear parasitemia.
Identifying the targets and properties of antibodies to PfEMP1 that are associated with protection from life
threatening malaria in African children will be key to developing tailored vaccines or therapeutics to prevent or
treat severe malaria. Discovering key protective antibody responses across ...

## Key facts

- **NIH application ID:** 10889106
- **Project number:** 5R01AI165595-03
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** Stephen Rogerson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $516,591
- **Award type:** 5
- **Project period:** 2022-08-15 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10889106

## Citation

> US National Institutes of Health, RePORTER application 10889106, Identifying functional antibody responses that protect against malaria in children (5R01AI165595-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10889106. Licensed CC0.

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