Primate malaria parasites as surrogate models to study invasion-blocking antibodies targeting Plasmodium vivax reticulocyte-binding protein 2b

Malaria caused by Plasmodium vivax, the most common form of the disease in the Americas, continues to be a major public health problem, including in Brazil. To develop new strategies for the control and treatment of vivax malaria, it is essential to obtain a better understanding of the mechanisms of invasion of red blood cells by the parasite. One of the main ligand-receptor interactions involves P. vivax reticulocyte-binding protein 2b (PvRBP2b), a member of the reticulocyte-binding protein (RBP) family, and transferrin receptor 1 (TfR1 or CD71), expressed on reticulocytes. Murine monoclonal antibodies against PvRBP2b can inhibit the PvRBP2b-TfR1 interaction and partially block reticulocyte invasion by P. vivax. Human anti-PvRBP2b monoclonal antibodies can inhibit receptor binding, but a recent study showed that murine and human anti-PvRBP2b monoclonals may not be able to block RBC invasion ex vivo. These negative results were not associated with the high PvRBP2b polymorphism found in the clinical isolates tested. Studies of RBC invasion by P. vivax are challenging due to the lack of continuous in vitro culture, but primate malaria parasites closely related to P. vivax—such as P. knowlesi and P. cynomolgi, which can be maintained in culture—provide an excellent model for in vitro experiments. The homologous RBP2b protein of P. cynomolgi has 77% identity, at the amino acid level, with RBP2b from the P. vivax Salvador 1 strain (PVX_094255), and this high similarity allows us to test wild-type parasites in invasion-blocking assays with antibodies to the P. vivax protein. Although P. knowlesi lacks members of the RBP family, this parasite expresses two proteins related to the Reticulocyte Binding Protein-like (RBL) family, the normocyte-binding proteins Xa and Xb (NBPXa and NBPXb). This project will: (1) replace the rbp2b and nbpx genes of P. cynomolgi and P. knowlesi, respectively, with the region of the P. vivax rbp2b gene encoding the TfR1-binding domain, (2) test whether genetically modified parasites have increased tropism for human reticulocytes, and (3) test whether anti-PvRBP2b antibodies can inhibit RBC invasion by intact and genetically modified P. cynomolgi, and by genetically modified P. knowlesi. This project will standardize a robust in vitro model system to investigate mechanisms underlying RBC invasion by P. vivax that can be explored in our laboratory in São Paulo. 

Project Details

Genetics and Genomics
Immunology
P. vivax

Jun 2025 — May 2026

Brazil

mAbs for malaria vaccine development