Development of Diagnostic Antibodies for Acute and Chronic Chagas Disease

/Abstract Chagas disease, caused by infection with the parasite Trypanosoma cruzi, has been deemed the most neglected of neglected tropical diseases. The parasite is transmitted to humans by bloodsucking insects that usually live in cracks in the walls of mud and straw houses common to poor rural and urban communities. It can also be transmitted through blood transfusion and mother-to-child transmission, which is increasingly common. An estimated 10 million people are infected and 30-40% of those will develop severe and often fatal heart disease due to the infection. High rates of immigration from Latin America have brought many people who are unknowingly infected into the US, where doctors are unfamiliar with the disease. Most people are infected as children, a time when infection is “brilliantly treatable”, but only an estimated 1% of patients are treated. This is due, in large part, to the lack of an effective means to diagnose infection. Infection can only be diagnosed by blood sampling but the quality of rapid diagnostic tests currently available is poor. Multiple public health organizations have identified the development of high-quality point-of-care rapid diagnostic tests for Chagas as an urgent need. Here, we propose to generate a panel of antibodies that can detect T. cruzi, markers that circulate in the blood during infection. We have identified 3 candidate diagnostic T. cruzi Ags that are present in blood and highly conserved among all T. cruzi strains. Here, we will generate antibodies specific for these targets, determine their binding characteristics, and test their ability to detect these markers in blood serum obtained from dogs, non-human primates, and humans that acquired T. cruzi through natural infections. Antibodies that display good diagnostic accuracy in these studies will be selected for further characterization and development in future studies, so that they can be deployed in new high-sensitivity point-of-care diagnostic tests for Chagas Disease. We have previously used these procedures to develop a point-of-care diagnostic assay for Ebola virus that displays a sensitivity better than the current gold standard, PCR. The successful completion of these studies will result in the first antibodies diagnostic for T. cruzi infection, allowing construction of the first point-of-care assay that can detect markers of Chagas Disease in the blood. This work will thus markedly improve our ability to diagnose Chagas Disease, allowing early treatment and improved management of those who are infected. Project Number: 1R21AI180397-01A1 | Fiscal Year: 2025 | NIH Institute/Center: National Institute of Allergy and Infectious Diseases (NIAID) | Principal Investigator: MICHAEL GUNN | Institution: DUKE UNIVERSITY, DURHAM, NC | Award Amount: $449,408 | Activity Code: R21 | Study Section: Etiology, Diagnostic, Intervention and Treatment of Infectious Diseases Study Section[EDIT] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R21AI18039701A1