# Parasite variant surface antigen expression and immune gaps in severe malaria

> **NIH NIH R21** · UNIVERSITY OF MARYLAND BALTIMORE · 2024 · $252,213

## Abstract

PROJECT SUMMARY
Severe malaria kills hundreds of thousands of children across sub-Saharan Africa annually, accounting for most
malaria-related deaths globally. We have not yet identified the exact parasite genes responsible for severe
disease that could be targets for vaccine or drug development. Parasite variant surface antigens – genetically
diverse malaria proteins expressed on the surface of infected erythrocytes - appear to play a critical role in severe
malaria pathogenesis. We recently developed a novel strategy to de novo sequence variant surface antigen
transcripts from whole blood using RNA-seq with a custom capture array to enrich for variant surface antigen
detection. Our newly developed capacity to determine full-length transcripts present in severe malaria infections
enables comprehensive identification of gene expression signatures for clinical syndromes and for comparisons
of such signatures across severe malaria subtypes and different geographies. Using this approach in Mali, we
have identified parasite variant surface antigens expressed solely in severe disease and other variant surface
antigens differentially expressed in severe versus mild disease that are known to target multiple human host
receptors. Our central hypothesis is that severe malarial disease is the result of a subset of virulent parasite
variant surface antigens that are common across sub-Saharan Africa. We will sequence the variant surface
antigen transcripts in severe malaria cases and matched uncomplicated malaria controls in Zambian children
and adults (Aim 1). We will then use a custom protein microarray featuring a comprehensive representation of
variant surface antigens to determine the malaria parasite variant surface antigens associated with increased
vulnerability to severe malarial in Zambian children and adults (Aim 2). This microarray will be populated with
severe disease variant surface antigens from Zambia sequenced in Aim 1, from Mali and Malawi (previously
sequenced), and from reference strains, as well as a broad selection of additional reactive malaria antigens from
all parasite lifecycle stages. We will determine whether the pathogenic variant surface antigens associated with
severe malaria in Zambians are similar to those previously identified in Malian children. The data generated from
this R21 study will be used to form the basis of an R01 proposal to identify common subsets of parasite variant
surface antigens associated with severe malaria in children and adults across Africa that could form the basis of
a vaccine or biologic.

## Key facts

- **NIH application ID:** 10987103
- **Project number:** 1R21AI180502-01A1
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Matthew Michael Ippolito
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $252,213
- **Award type:** 1
- **Project period:** 2024-07-09 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10987103

## Citation

> US National Institutes of Health, RePORTER application 10987103, Parasite variant surface antigen expression and immune gaps in severe malaria (1R21AI180502-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10987103. Licensed CC0.

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