Plasmodium vivax Invasion Pathways into Human Reticulocytes – VIPeRs
This project aims to:
- identify P. vivax ligands involved in host cell invasion; and
- understand how P. vivax has gained the capacity to infect reticulocytes from Duffy-negative individuals
This application seeks to combine state-of-the-art genomic and biological approaches to characterize P. vivax invasion pathways involved in human Duffy-negative and Duffy-positive reticulocytes. Understanding these host-parasite interactions is key to estimate the risk of emergence of vivax malaria in Africa and to develop novel intervention strategies such as vaccines against this pathogen.
P. vivax remains a major public health problem in developing countries. Like the other Plasmodium species, P. vivax has a complex life cycle involving multiple stages in the mosquito vector and human host. For instance, erythrocyte invasion is a complex process involving multiple interactions between Plasmodium merozoites and host erythrocytes. Unlike P. falciparum, which can use multiple erythrocyte receptors for invasion and has merozoite proteins with overlapping and redundant receptor-binding functions, invasion of human erythrocytes by P. vivax merozoites primarily relies on the interaction between the P. vivax Duffy Binding Protein (PvDBP) and the erythrocyte Duffy antigen receptor for chemokines (DARC). Consequently, PvDBP is considered a promising candidate for a P. vivax malaria vaccine. However, recently, a growing body of studies have reported PCR-positive vivax malaria cases in Duffy-negative individuals around the world, specifically across Africa and South America. These novel observations highlight the emerging issue of P. vivax infection in Duffy-negative populations, which questions the essential role of the PvDBP-DARC interaction and raises the possibility of alternative invasion mechanism(s), which have implications for the design of effective blood-stage vaccine candidates for P. vivax malaria.