Parasite variant surface antigen expression and immune gaps in severe malaria
Active Project Grant Awarded Last action
- Award ID
- R21AI180502
- Recipient
-
University Of Maryland, Baltimore UEI Z9CRZKD42ZT1
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $675,541
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date 78% complete
- Originally
- Place of performance
- Baltimore, MD 21201, USA
Award details come from USAspending.gov.
Description
- Abstract
- 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.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $0 | |
| Amendment | $196,337 | |
| Amendment | $25,222 | |
| Amendment | $226,991 | |
| Original award | $226,991 |
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| The Johns Hopkins University | $65,038 | |
| The Johns Hopkins University | $69,945 |
Quick answers
Who received award R21AI180502?
R21AI180502 was awarded to University Of Maryland, Baltimore by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on July 9, 2024.
How much is award R21AI180502 worth?
$675,541 has been obligated on R21AI180502.
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