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In Vitro Drug Screening Against All Life Cycle Stages of Trypanosoma cruzi Using Parasites Expressing β-galactosidase
Published on: November 5, 2021
RIG-I-Adjuvanted Immunogen Elicited T-Cell Immunity Controls Trypanosoma cruzi, Chagasic Cardiomyopathy, and Left
Nandadeva Lokugamage1, Allison Wyrick1, Subhadip Choudhuri1
1Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
New immunogens, bicistronic immunogen with RIG-I adjuvant (BCV) and without (BCVR), effectively control Trypanosoma cruzi. These safe treatments prevent heart failure and sudden death in Chagas disease.
Area of Science:
- Immunology
- Parasitology
- Cardiovascular Medicine
Background:
- Chagas disease, caused by Trypanosoma cruzi, leads to severe cardiac complications including heart failure and sudden death.
- Current treatments for Chagas disease are limited and often toxic.
- Myocarditis and cardiac fibrosis are key pathological features contributing to Chagas disease-related heart failure.
Purpose of the Study:
- To develop and evaluate novel bicistronic immunogens (BCV and BCVR) for the treatment of Trypanosoma cruzi infection.
- To assess the safety and efficacy of BCV and BCVR in controlling parasite replication and preventing cardiac pathology.
- To investigate the potential of these immunogens in mitigating heart failure and sudden death associated with Chagas disease.
Main Methods:
- Design of bicistronic immunogens (BCV with RIG-I adjuvant, BCVR without) adhering to FDA guidelines.
- Assessment of immunogen toxicity and safety profiles.
- Evaluation of immunogen efficacy in controlling Trypanosoma cruzi replication and persistence.
- Analysis of cardiac pathology, including myocarditis, fibrosis, and left ventricular function.
Main Results:
- BCV and BCVR immunogens were found to be nontoxic.
- Both immunogens demonstrated high efficacy in controlling Trypanosoma cruzi replication and persistence.
- BCV/BCVR treatment successfully blocked the development of myocarditis, cardiac fibrosis, and left ventricular dysfunction.
- The immunogens prevented heart failure and sudden death in the context of Chagas disease.
Conclusions:
- BCV and BCVR represent safe and highly effective immunotherapeutic strategies against Trypanosoma cruzi.
- These novel immunogens hold significant promise for preventing the progression of Chagas disease and its life-threatening cardiac manifestations.
- Further clinical development of BCV and BCVR could offer a new therapeutic avenue for patients with Chagas disease.
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