High-throughput analysis of dynamics of antibody responses against defined epitopes: prioritization of diagnostic and prognostic markers for chagas disease - 1 project summary / abstract 2 3…

The National Institute of Allergy and Infectious Diseases (NIAID) awarded Fundacion Instituto De Investigaciones Biotecnologicas a Project Grant of $133,746 under the Allergy and Infectious Diseases Research program (CFDA 93.855) effective September 9, 2025, with completion scheduled for August 31, 2030. This research initiative conducts high-throughput analysis of antibody response dynamics against defined epitopes of Trypanosoma cruzi to identify and prioritize diagnostic and prognostic biomarkers for Chagas disease. The research addresses a critical clinical need to develop earlier, more reliable endpoints for assessing treatment success in clinical trials, as current serological methods requiring long-term patient follow-ups present significant obstacles to drug development and validation.

The project leverages an established atlas of antigens and epitopes for Chagas disease to advance understanding of antibody seroprevalence patterns across diverse patient populations. By identifying biomarkers that enable earlier determination of treatment efficacy or failure, the research aims to facilitate more efficient drug development pathways and improve diagnostic capabilities for this endemic parasitic disease affecting populations throughout the Americas. The work will be conducted in Argentina by the Buenos Aires-based institute, which specializes in parasitological research and infectious disease investigation through advanced molecular biology and genomics methodologies.

High-throughput analysis of dynamics of antibody responses against defined epitopes: prioritization of diagnostic and prognostic markers for chagas disease - 1 project summary / abstract 2 3 trypanosoma cruzi is a parasite responsible for an important human disease, chagas disease, which 4 is endemic in the americas. The parasite is transmitted by the bite of an insect, or by blood transfusion 5 or organ transplants. Current treatment is limited to two nitro-heterocyclic drugs, which can cure the 6 disease in its acute phase, and provide benefits to patients in the chronic stage, but they have 7 unwanted adverse effects. New drugs and treatments are being explored, but certification of cure in 8 clinical trials is difficult to achieve. Management of this disease rests heavily on the use of diagnostic 9 tools: either molecular detection of parasite DNA by PCR or circulating antibodies against parasite 10 proteins or protein fragments. Detection of parasite DNA is difficult in the chronic stage of the disease 11 where parasitemia is low or undetectable, and hence requires serial blood sampling and PCR 12 replicates to achieve reliable detection. In contrast, serological assays readily detect infections, and 13 reduction in antibody levels (seroconversion or trend to seroconversion) have been historically used 14 as primary endpoints in clinical trials with some success but requiring long follow-UPS of patients. A 15 major unmet need in this area is thus the ability to produce earlier informative outcomes for treatment 16 success or failure. This constitutes a major obstacle in current drug trials. For this, a constant stream 17 of new biomarkers is required to explore their potential at these tasks. One of the most promising 18 developments in the field was the construction of an atlas of antigens and epitopes for chagas 19 disease, providing extensive information on the seroprevalence of defined epitopes across diverse 20 populations of infected patients. Using a large set of antigens identified in this atlas, we are beginning 21 to obtain valuable information on how individual antibody repertoires of patients in a clinical trial 22 respond to treatments. In this application we build on this previous work and propose to characterize 23 the dynamics of the human antibody response against this parasite. Using peptide microarrays 24 displaying selected trypanosoma cruzi peptide antigens we will investigate these dynamics in an 25 expanded set of retrospective samples from diverse patient populations. We will use this information 26 to prioritize serology markers for applications seeking to monitor disease status or progression. With 27 this set of prioritized antigens, we will produce proof-of-principle immunoassays for use in clinical 28 settings.