Last Updated: 22/10/2024
Defining acquired immunity in symptomatic and asymptomatic Plasmodium vivax infections using single-cell RNA sequencing
Objectives
The main objective of the project is to identify critical aspects of the human adaptive immune response that contribute to the asymptomatic state of P. vivax infection by studying the transcriptomic profile of T and B cells in these individuals and comparing it to that of individuals who develop the symptomatic form and healthy uninfected controls.
Malaria mainly affects disadvantaged populations and causes significant economic losses. In the Americas, most cases are caused by P. vivax (Pv) and, although the incidence of malaria has declined recently, it remains endemic in 17 countries and territories, with the Amazon contributing 90% of cases. One of the challenges to achieving malaria control is that most Pv-infected humans are asymptomatic, but remain infectious to vectors, contributing to local transmission and endemicity. Pv infections trigger adaptive, humoral, and cellular immune responses that are essential to control parasitemia, rendering most hosts clinically immune by confining/controlling the parasite and disease signs and symptoms. However, host-acquired immune responses often cannot eliminate Pv infection and/or prevent reinfection. Our main objective is to identify critical aspects of the human adaptive immune response that contribute to the asymptomatic state of Pv infection (ASY) by comparing it to patients who develop the symptomatic form (SYM) and uninfected healthy controls (CTL). Understanding the particularities of the immune response during ASY Pv infections and the factors contributing to its occurrence will support effective malaria elimination strategies. In this project we aim to: (i) define ex vivo B and T cell receptor populations and repertoire in ASY and SYM patients infected by P. vivax in comparison with CTLs resident in the Peruvian Amazon. The expression of markers in cells of the adaptive immune response and the production of selected immune molecules will contribute to our knowledge of human resistance/susceptibility to P. vivax malaria.
Cross-sectional study.
Sep 2024 — Sep 2027