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NIH grant 1R01AI201572-01: Integrated Genomic and Immunoproteomic Strategy for Development of a Next-Generation Chagas Disease Diagnostic Assay
Institute: {'code': 'AI', 'abbreviation': 'NIAID', 'name': 'National Institute of Allergy and Infectious Diseases', 'admin_org_id': '12500003', 'admin_funding_url': ''}. PI: Jeffrey Dominick Whitman. Award: $770203.
Start: 2026-09-25T00:00:00.
PROJECT SUMMARY/ABSTRACT
Infection by Trypanosoma cruzi, the etiologic agent of Chagas disease, results in cardiac and gastrointestinal
diseases after decades of parasite persistence. Diagnosis in the chronic phase relies on serological detection
of anti-T. cruzi antibodies. A major limitation of current serology is variable test performance across infected
endemic populations from Latin America. In direct comparisons, serological reactivity is lowest in Mexico and
intermediate in Central America, compared to South America. Other studies have shown discordant serology
results, where commercial assays are negative or weakly positive, but immunoassays using local T. cruzi
lysates demonstrate greater reactivity. This pattern broadly parallels the geographic distribution of T. cruzi
discrete typing units (DTUs), but intra-DTU genetic variation may also be important. Antigens in commercial
diagnostics have largely been derived from South American T. cruzi isolates raising questions about their
applicability in endemic areas to the north. To date, no studies have critically examined the link between
parasite genotypic differences and serological reactivity and discordance in specimens from across the
endemic zone. Our objective is to develop a highly accurate, novel immunoassay that eliminates the need for
confirmatory testing in most patients. We propose to accomplish this objective via the innovative techniques of
Aim 1) generating high-quality reference genomes for T. cruzi DTUs by leveraging capture enrichment
sequencing and selective genome amplification for identification of contemporary T. cruzi strains and Aim 2)
employing innovative antigen discovery methods to identify common conserved immunogenic epitopes across
all infected populations. Our approach combines innovative molecular biology techniques to directly compare
regional biology of parasite antigens to host humoral responses, and will have direct translational potential for
diagnostic and epidemiological goals.document fetched 2026-10-04 02:44