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

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2021 · $354,605

## Abstract

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 again...

## Key facts

- **NIH application ID:** 10201738
- **Project number:** 5R01HL146377-03
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Mark A Travassos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $354,605
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201738

## Citation

> US National Institutes of Health, RePORTER application 10201738, Malaria variant surface antigen expression and vulnerability to disease in Malian children with Hemoglobin C trait (5R01HL146377-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10201738. Licensed CC0.

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