Project Lead(s): Deepak Gaur
Plasmodium vivax malaria is geographically the most widespread malarial disease across the world.
While generally considered to be benign, a number of reports have shown P. vivax malaria can be severe.
The project sought to generate crucial novel data on the biochemical and functional characterization of the P. vivax reticulocyte binding protein (PvRBP) antigens – potent targets for a P. vivax vaccine.
While, the mechanisms underlying the red cell invasion process of P. falciparum have been studied in great detail, similar studies on P. vivax have been lacking.
P. vivax invades a small subset of young, immature red cells known as reticulocytes, which constitute up to 1% of human blood. A central dogma of P. vivax invasion is that it is completely dependent on the interaction between the duffy receptor on reticulocytes with its parasite ligand, the duffy binding protein (DBP).
However, P. vivax appears to have evolved alternate invasion pathways, as a number of studies have reported P. vivax infections among duffy-negative individuals.
In light of these reports, it is crucial to validate novel vaccine target antigens of P. vivax (other than DBP), to counter the parasites that no longer exhibit the total dependence of the duffy interaction for invasion.
In this regard, the P. vivax genome and transcriptome has highlighted a family of proteins known as PvRBPs that have been implicated in reticulocyte-specific invasion.
Results from this project generated crucial new data on the biochemical and functional characterization of the PvRBPs, and validated them as potent targets for a putative P. vivax vaccine.
Research showed that PvRBP antigens appear to be potent targets of antibody mediated blockade of reticulocyte invasion by P. vivax, and establishes a proof of principle for vaccine development.
The team also identified and produced functional reticulocyte-binding domains of the P. vivax, established a short-term, in vitro culture for P. vivax and assayed the invasion inhibitory activity of the specific antibodies raised against the PvRBP antigens of interest.
Data from this work has been presented in conferences.