Description
- Abstract:
- Malaria continues to be a global burden and one of the leading causes of child mortalities in endemic Sub-Saharan Africa. Malaria largely affects populations of low socioeconomic backgrounds who do not have consistent access to treatment. A vaccine is much needed to stop the spread of the disease, especially with resistance to treatment and control measures on the rise. Previous vaccine efforts have not yielded high efficacy or promising results, particularly for severe malaria, which has a large fatality rate of 30%. There is growing evidence that the epidemiology of severe malaria is unique, with patients naturally acquiring immunity after only one or two episodes of severe malaria, and this protection is distinguished from responses that control parasitemia. New vaccine targets are much needed to address this gap. Here, we use a whole proteome differential screening using serum from children pre and post-susceptible to severe malarial anemia, before and after they develop resistance to severe malaria and the acute vs convalescent phase of cerebral malaria. After three rounds of biopanning, we generated a diverse list of genes uniquely expressed by children post-susceptible to severe malarial anemia or after developing resistance. Our screens lead us to PfP113, a protein with limited sequence variation that plays a role in anchoring Rh5 to the merozoite surface. We show that antibodies to PfP113 inhibit parasite growth. From our resistant screen, we selected a conserved protein that is still unknown but has interesting properties worth further investigating. Our approach allowed us to discover new antigen targets uniquely expressed after an episode of severe malarial anemia, after developing resistance to severe malaria, and during cerebral malaria. Thus we expand on the limited repertoire of antigen targets for a blood-stage vaccine, specifically against severe malaria.
- Notes:
- Thesis (Sc. M.)--Brown University, 2025
Citation
Chebli Fawaz, Rim,
"Identifying the Parasite Targets Mediating Resistance to Severe Malaria"
(2025).
Biotechnology, Biology and Medicine Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://repository.library.brown.edu/studio/item/bdr:j4dq38as/
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Biology and Medicine Theses and Dissertations
Theses and Dissertations for the Biology and Medicine department....