ArticlePLoS neglected tropical diseases2022
Vaccine-linked chemotherapy with a low dose of benznidazole plus a bivalent recombinant protein vaccine prevents the development of cardiac fibrosis caused by Trypanosoma cruzi in chronically-infected BALB/c mice.
Article in PLoS neglected tropical diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 24 citations in OpenAlex.
- Treatment with low-dose bicistronic immunotherapy mitigates parasite persistence and improves serological and cardiac outcomes in adult mice infected withEmerging microbes & infections · 2026Article
- Vaccines against chronicExpert review of vaccines · 2026Review
- Long-Lasting Antibody and CD8Vaccines · 2026Article
- Epitope mapping of vaccine antigens Tc24 and TSA1 with antibodies from Trypanosoma cruzi-infected patients.Genes and immunity · 2026Article
- RIG-I-Adjuvanted Immunogen Elicited T-Cell Immunity Controls Trypanosoma cruzi, Chagasic Cardiomyopathy, and Left Ventricular Dysfunction.JACC. Basic to translational science · 2026Article
- Randomized field trial of a therapeutic vaccine against Trypanosoma cruzi natural infection in dogs and correlates for efficacy.NPJ vaccines · 2025Article
- Fighting Strategies Against Chagas' Disease: A Review.Pathogens (Basel, Switzerland) · 2025Review
- An Update on Vaccines AgainstPathogens (Basel, Switzerland) · 2025Review
- Immunomodulatory activity of Trypanosoma cruzi recombinant antigen combination TSA-1-C4 and Tc24-C4 induce activation of macrophages and CD8Parasitology research · 2025Article
- Chagas Disease: A Silent Threat for Dogs and Humans.International journal of molecular sciences · 2024Review
- Localized cardiac small molecule trajectories and persistent chemical sequelae in experimental Chagas disease.Nature communications · 2023Article
- The Low Variability of Tc24 inPathogens (Basel, Switzerland) · 2023Article
- Vaccine-linked chemotherapy improves cardiac structure and function in a mouse model of chronic Chagas disease.Frontiers in cellular and infection microbiology · 2023Article
- Signature of cardiac alterations in early and late chronic infections with Trypanosoma cruzi in mice.PloS one · 2023Article
- Future Impact of mRNA Therapy on Cardiovascular Diseases.Methodist DeBakey cardiovascular journal · 2022Review
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChagas disease (CD) is caused by Trypanosoma cruzi and affects 6-7 million people worldwide. Approximately 30% of chronic patients develop chronic chagasic cardiomyopathy (CCC) after decades. Benznidazole (BNZ), one of the first-line chemotherapy used for CD, induces toxicity and fails to halt the progression of CCC in chronic patients. The recombinant parasite-derived antigens, including Tc24, Tc24-C4, TSA-1, and TSA-1-C4 with Toll-like receptor 4 (TLR-4) agonist-adjuvants reduce cardiac parasite burdens, heart inflammation, and fibrosis, leading us to envision their use as immunotherapy together with BNZ. Given genetic immunization (DNA vaccines) encoding Tc24 and TSA-1 induce protective immunity in mice and dogs, we propose that immunization with the corresponding recombinant proteins offers an alternative and feasible strategy to develop these antigens as a bivalent human vaccine. We hypothesized that a low dose of BNZ in combination with a therapeutic vaccine (TSA-1-C4 and Tc24-C4 antigens formulated with a synthetic TLR-4 agonist-adjuvant, E6020-SE) given during early chronic infection, could prevent cardiac disease progression and provide antigen-specific T cell immunity. METHODOLOGY/ PRINCIPAL
findingsWe evaluated the therapeutic vaccine candidate plus BNZ (25 mg/kg/day/7 days) given on days 72 and 79 post-infection (p.i) (early chronic phase). Fibrosis, inflammation, and parasite burden were quantified in heart tissue at day 200 p.i. (late chronic phase). Further, spleen cells were collected to evaluate antigen-specific CD4+ and CD8+ T cell immune response, using flow cytometry. We found that vaccine-linked BNZ treated mice had lower cardiac fibrosis compared to the infected untreated control group. Moreover, cells from mice that received the immunotherapy had higher stimulation index of antigen-specific CD8+Perforin+ T cells as well as antigen-specific central memory T cells compared to the infected untreated control.
conclusionsOur results suggest that the bivalent immunotherapy together with BNZ treatment given during early chronic infection protects BALB/c mice against cardiac fibrosis progression and activates a strong CD8+ T cell response by in vitro restimulation, evidencing the induction of a long-lasting T. cruzi-immunity.
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