Last Updated: 27/08/2024
Determination of the role of tryptophan-rich antigens during P. vivax reticulocyte invasion using a functional transgenic P. knowlesi model and P. vivax ex vivo assays
Objectives
*Original in Dutch: Bepaling van de rol van tryptophan-rich antigens tijdens de invasie van P. vivax reticulocyten door middel van een functioneel transgeen P. knowlesi model en P. vivax ex vivo assays.
Since the function of the P. vivax tryptophan-rich antigens (PvTRAgs) remains undescribed, the aim of this project is to characterize the involvement of five PvTRAg proteins during the process of erythrocyte invasion.
Plasmodium vivax is the most widespread species causing malaria in humans, but due to the lack of a long-term culture system, knowledge about the biology of this parasite is limited. An important step in P. vivax infection is the invasion process of reticulocytes (young red blood cells), which involves several host receptor-parasite ligand interactions. Description of P. vivax invasion ligands brings relevant information for vaccine development, essential for designing targeted control and prevention strategies. In vitro studies and transcriptome profiles of P. vivax isolates highlighted the potential invasion role of some PvTRAg proteins. In addition, their high immunogenicity and conserved sequence between isolates make them suitable as vaccine targets. In vitro studies will be performed that will evaluate the binding capacity of recombinant PVTRAg proteins to erythrocytes, and will create transgenic P. knowlesi lines to elucidate the role of the selected PvTRAgs and their P. knowlesi orthologs during invasion. Finally, the PvTRAg proteins showing strong evidence of being invasion ligands will be confirmed in ex vivo invasion assays with P. vivax isolates.
Nov 2023 — Oct 2027
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