Vaccine-Linked Chemotherapy Improves Benznidazole Efficacy for Acute Chagas Disease

Infect Immun. 2018 Mar 22;86(4):e00876-17. doi: 10.1128/IAI.00876-17. Print 2018 Apr.


Chagas disease affects 6 to 7 million people worldwide, resulting in significant disease burdens and health care costs in countries of endemicity. Chemotherapeutic treatment is restricted to two parasiticidal drugs, benznidazole and nifurtimox. Both drugs are highly effective during acute disease but are only minimally effective during chronic disease and fraught with significant adverse clinical effects. In experimental models, vaccines can be used to induce parasite-specific balanced TH1/TH2 immune responses that effectively reduce parasite burdens and associated inflammation while minimizing adverse effects. The objective of this study was to determine the feasibility of vaccine-linked chemotherapy for reducing the amount of benznidazole required to significantly reduce blood and tissue parasite burdens. In this study, we were able to achieve a 4-fold reduction in the amount of benznidazole required to significantly reduce blood and tissue parasite burdens by combining the low-dose benznidazole with a recombinant vaccine candidate, Tc24 C4, formulated with a synthetic Toll-like 4 receptor agonist, E6020, in a squalene oil-in-water emulsion. Additionally, vaccination induced a robust parasite-specific balanced TH1/TH2 immune response. We concluded that vaccine-linked chemotherapy is a feasible option for advancement to clinical use for improving the tolerability and efficacy of benznidazole.

Keywords: CD8+ T cell response; Chagas disease; E6020 adjuvant; Trypanosoma cruzi; benznidazole; recombinant protein vaccine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Chagas Cardiomyopathy / drug therapy
  • Chagas Cardiomyopathy / immunology
  • Chagas Cardiomyopathy / parasitology
  • Chagas Cardiomyopathy / pathology
  • Chagas Disease / drug therapy*
  • Chagas Disease / immunology*
  • Chagas Disease / parasitology
  • Cytokines / metabolism
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Humans
  • Immunohistochemistry
  • Nitroimidazoles / pharmacology
  • Nitroimidazoles / therapeutic use*
  • Parasite Load
  • Protozoan Vaccines / immunology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Trypanocidal Agents / pharmacology
  • Trypanocidal Agents / therapeutic use*
  • Trypanosoma cruzi / immunology
  • Vaccination


  • Cytokines
  • Epitopes, T-Lymphocyte
  • Nitroimidazoles
  • Protozoan Vaccines
  • Trypanocidal Agents
  • benzonidazole