Last Updated: 30/06/2025
Potential New Target for Plasmodium vivax Vaccines: Immune, Molecular, and Functional Study of a New Protein in Blood Shapes
Objectives
This project aims to produce and characterize – from the immunological, molecular and functional point of view – a newly described P.vivax protein, called erythrocyte binding protein 2 (EBP2). Specifically, the main objectives of the present proposal are:
- to produce the recombinant EBP2 and to evaluate its immunogenicity in an animal model;
- to evaluate the naturally acquired immunity in populations exposed to P. vivax infection;
- to evaluate the EBP2 genetic diversity in circulating parasites in Brazil;
- perform in vitro functional assays to assess the ability of EBP2 to interact with human reticulocytes and erythrocytes, as well as its ability to induce antibodies that block binding-receptor interaction.
Invasion of erythrocytes by malaria parasites ensures the success of human infection and, consequently, the development of clinical disease. In the case of Plasmodium vivax, the main candidate vaccine antigen is based on a classical concept that this parasite only invades erythrocytes expressing the DARC blood group antigen. However, the recent findings that P. vivax can invade erythrocytes by an alternative route, and still unknown, reinforce the hypothesis that the mechanism of invasion of this parasite is much more complex than originally thought. In this context, recent works of reassembly of the P. vivax genome have identified new genes that encode the blood stage proteins of this parasite. The hypothesis is that this protein may participate in or be the ligand involved in the invasion of P. vivax into negative DARC erythrocytes.
This proposal will benefit from previous field studies conducted by our research group in the Brazilian Amazon (cross-sectional and cohort), where different profiles of respondents to P. vivax have been identified. The proposal is also based on a solid and successful collaboration between the proponent (LH Carvalho) and the research group of Dr. JH Adams, South Florida University, USA, where student exchange has been constant. It is expected to combine the strengths of each of these research groups to make important contributions to clarify aspects of parasite biology as well as to identify candidate vaccine antigens. Finally, the proposal is considered relevant not only from a scientific point of view, but involves technological innovation, including the development of vaccine prototypes and platform enhancement for the production of high quality recombinant proteins in CPqRR.
Jun 2017 — May 2020
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