Antibody biomarker discovery for current and recent asymptomatic malaria exposure

Objectives

This work proposes to leverage the diversity in serological markers to identify informative antibody biomarkers to estimate malaria exposure. Based on preliminary data, the central hypothesis of this proposal is that individuals exposed to low-density malaria infections have unique serological profiles that can be used for rapid evaluation of recent and current exposure.

This hypothesis will be tested with the following specific aims:

• Aim 1: Identify antibody biomarkers for current and recent (6 months) subclinical Plasmodium falciparum and Plasmodium vivax exposure. Antibody biomarkers will be identified by measuring seroreactivity of matched exposed and unexposed individuals on novel ultra-dense peptide arrays populated with sequences from Plasmodium falciparum and Plasmodium vivax antigen variants from both reference strains and geographically- relevant field isolates.
• Aim 2: Validate novel peptide targets against malaria antigens using a multiplexed bead-based immunoassay format. Down-selected peptides will be synthesized in bulk and conjugated to barcoded magnetic beads for a multiplexed fluorescence-based immunoassay. Seroreactivity to peptide targets will be measured on well-characterized samples from individuals with known malaria exposure as well as endemic controls.

The proposed work is the first step toward developing a robust point-of-contact test that can be used to characterize malaria transmission and risk, ultimately enabling better and more precise targeting of interventions.