A therapeutic vaccine prototype induces protective immunity and reduces cardiac fibrosis in a mouse model of chronic Trypanosoma cruzi infection

PLoS Negl Trop Dis. 2019 May 30;13(5):e0007413. doi: 10.1371/journal.pntd.0007413. eCollection 2019 May.


Chagas disease, caused by the parasite Trypanosoma cruzi, develops into chronic Chagas' cardiomyopathy in ~30% of infected individuals, characterized by conduction disorders, arrhythmias, heart failure, and even sudden cardiac death. Current anti-parasitic treatments are plagued by significant side effects and poor efficacy in the chronic phase of disease; thus, there is a pressing need for new treatment options. A therapeutic vaccine could bolster the protective TH1-mediated immune response, thereby slowing or halting the progression of chronic Chagas' cardiomyopathy. Prior work in mice has demonstrated therapeutic efficacy of a Tc24 recombinant protein vaccine in the acute phase of Chagas disease. However, it is anticipated that humans will be vaccinated therapeutically when in the chronic phase of disease. This study investigates the therapeutic efficacy of a vaccine prototype containing recombinant protein Tc24, formulated with an emulsion containing the Toll-like receptor 4 agonist E6020 as an immunomodulatory adjuvant in a mouse model of chronic T. cruzi infection. Among outbred ICR mice vaccinated during chronic T. cruzi infection, there is a significant increase in the number of animals with undetectable systemic parasitemia (60% of vaccinated mice compared to 0% in the sham vaccine control group), and a two-fold reduction in cardiac fibrosis over the control group. The vaccinated mice produce a robust protective TH1-biased immune response to the vaccine, as demonstrated by a significant increase in antigen-specific IFNγ-production, the number of antigen-specific IFNγ-producing cells, and IgG2a antibody titers. Importantly, therapeutic vaccination significantly reduced cardiac fibrosis in chronically infected mice. This is a first study demonstrating therapeutic efficacy of the prototype Tc24 recombinant protein and E6020 stable emulsion vaccine against cardiac fibrosis in a mouse model of chronic T. cruzi infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Protozoan / immunology*
  • Chagas Cardiomyopathy / immunology*
  • Chagas Cardiomyopathy / parasitology
  • Chagas Cardiomyopathy / pathology
  • Chagas Cardiomyopathy / prevention & control
  • Disease Models, Animal
  • Female
  • Fibrosis
  • Humans
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Mice
  • Mice, Inbred ICR
  • Myocardium / pathology
  • Parasitemia / immunology
  • Parasitemia / parasitology
  • Parasitemia / pathology
  • Parasitemia / prevention & control
  • Protozoan Vaccines / administration & dosage*
  • Protozoan Vaccines / immunology
  • Th1 Cells / immunology
  • Trypanosoma cruzi / immunology
  • Trypanosoma cruzi / physiology
  • Vaccination


  • Antibodies, Protozoan
  • Protozoan Vaccines
  • Interferon-gamma

Grant support

This work was funded by the Carlos Slim Foundation (http://fundacioncarlosslim.org/english/salud/) and the the Global Health Innovation Technology Fund (G2014-002)(https://www.ghitfund.org/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.