ArticlePLoS pathogens2015
A human type 5 adenovirus-based Trypanosoma cruzi therapeutic vaccine re-programs immune response and reverses chronic cardiomyopathy.
Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 90 citations in OpenAlex.
- Promiscuous Recognition of a Trypanosoma cruzi CD8+ T Cell Epitope among HLA-A2, HLA-A24 and HLA-A1 Supertypes in Chagasic Patients.PloS one · 2016Trial
- A novel replication-deficient feline herpesvirus type 1 vector-based vaccine provides strong immune protection in cats.Journal of virology · 2026Article
- Randomized field trial of a therapeutic vaccine against Trypanosoma cruzi natural infection in dogs and correlates for efficacy.NPJ vaccines · 2025Article
- Heterologous prime-boost immunization based on a human adenovirus 5 vectored containing Trichinella spiralis Cystatin-like protein elicits protective mucosal immunity in mice.PLoS neglected tropical diseases · 2025Article
- The time has come for a vaccine against Chagas disease.Lancet regional health. Americas · 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
- Research advances in replication-deficient viral vector vaccines.Frontiers in veterinary science · 2025Review
- RNA and protein immunization withFrontiers in cellular and infection microbiology · 2025Article
- Nasal vaccination againstFrontiers in immunology · 2025Article
- Influence of angiotensin II type 1 receptors and angiotensin-converting enzyme I/D gene polymorphisms on the progression of Chagas' heart disease in a Brazilian cohort: Impact of therapy on clinical outcomes.PLoS neglected tropical diseases · 2024Article
- The beneficial effect of fluoxetine on behavioral and cognitive changes in chronic experimental Chagas disease unveils the role of serotonin fueling astrocyte infection by Trypanosoma cruzi.PLoS neglected tropical diseases · 2024Article
- Harnessing RNA Technology to Advance Therapeutic Vaccine Antigens against Chagas Disease.ACS applied materials & interfaces · 2024Article
- Neglected tropical disease (NTD) diagnostics: current development and operations to advance control.Pathogens and global health · 2024Review
- mRNA and Adenoviral Vector Vaccine Platforms Utilized in COVID-19 Vaccines: Technologies, Ecosystem, and Future Directions.Vaccines · 2023Review
- ASP-2/Trans-sialidase chimeric protein induces robust protective immunity in experimental models of Chagas' disease.NPJ vaccines · 2023Article
- Immunization with a Trypanosoma cruzi cyclophilin-19 deletion mutant protects against acute Chagas disease in mice.NPJ vaccines · 2023Article
- Genetic Ablation and Pharmacological Blockade of Bradykinin B1 Receptor Unveiled a Detrimental Role for the Kinin System in Chagas Disease Cardiomyopathy.Journal of clinical medicine · 2023Article
- Recent Advances in the Development of Adenovirus-Vectored Vaccines for Parasitic Infections.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Signature of cardiac alterations in early and late chronic infections with Trypanosoma cruzi in mice.PloS one · 2023Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is a prototypical neglected tropical disease. Specific immunity promotes acute phase survival. Nevertheless, one-third of CD patients develop chronic chagasic cardiomyopathy (CCC) associated with parasite persistence and immunological unbalance. Currently, the therapeutic management of patients only mitigates CCC symptoms. Therefore, a vaccine arises as an alternative to stimulate protective immunity and thereby prevent, delay progression and even reverse CCC. We examined this hypothesis by vaccinating mice with replication-defective human Type 5 recombinant adenoviruses (rAd) carrying sequences of amastigote surface protein-2 (rAdASP2) and trans-sialidase (rAdTS) T. cruzi antigens. For prophylactic vaccination, naïve C57BL/6 mice were immunized with rAdASP2+rAdTS (rAdVax) using a homologous prime/boost protocol before challenge with the Colombian strain. For therapeutic vaccination, rAdVax administration was initiated at 120 days post-infection (dpi), when mice were afflicted by CCC. Mice were analyzed for electrical abnormalities, immune response and cardiac parasitism and tissue damage. Prophylactic immunization with rAdVax induced antibodies and H-2Kb-restricted cytotoxic and interferon (IFN)γ-producing CD8+ T-cells, reduced acute heart parasitism and electrical abnormalities in the chronic phase. Therapeutic vaccination increased survival and reduced electrical abnormalities after the prime (analysis at 160 dpi) and the boost (analysis at 180 and 230 dpi). Post-therapy mice exhibited less heart injury and electrical abnormalities compared with pre-therapy mice. rAdVax therapeutic vaccination preserved specific IFNγ-mediated immunity but reduced the response to polyclonal stimuli (anti-CD3 plus anti-CD28), CD107a+ CD8+ T-cell frequency and plasma nitric oxide (NO) levels. Moreover, therapeutic rAdVax reshaped immunity in the heart tissue as reduced the number of perforin+ cells, preserved the number of IFNγ+ cells, increased the expression of IFNγ mRNA but reduced inducible NO synthase mRNA. Vaccine-based immunostimulation with rAd might offer a rational alternative for re-programming the immune response to preserve and, moreover, recover tissue injury in Chagas' heart disease.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.