Assessment of a combined treatment with a therapeutic vaccine and benznidazole for the Trypanosoma cruzi chronic infection

•A new vaccine formulation named TSNt-ISPA was developed against T. cruzi infection.•A therapeutic vaccine treatment was assessed in two chronic infection mouse models.•A mixed vaccine-Benznidazole treatment was assessed in the both mouse models.•The therapeutic administration of TSNt-ISPA decreased...

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Bibliographic Details
Published in:Acta tropica Vol. 229; p. 106334
Main Authors: Prochetto, Estefanía, Bontempi, Iván, Rodeles, Luz, Cabrera, Gabriel, Vicco, Miguel, Cacik, Paula, Pacini, María Florencia, Pérez Gianeselli, Mónica, Pérez, Ana Rosa, Marcipar, Iván
Format: Journal Article
Language:English
Published: Netherlands Elsevier B.V 01-05-2022
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Summary:•A new vaccine formulation named TSNt-ISPA was developed against T. cruzi infection.•A therapeutic vaccine treatment was assessed in two chronic infection mouse models.•A mixed vaccine-Benznidazole treatment was assessed in the both mouse models.•The therapeutic administration of TSNt-ISPA decreased cardiac lessions.•Mixed therapeutic administration of TSNt-ISPA and Benznidazole improved the treatment. The difficulties encountered in achieving treatments for chronic Chagas disease have promoted the investigation of new therapeutic strategies. In this study, we used two murine models of Trypanosoma cruzi chronic infection to determine the usefulness of applying a therapeutic vaccine alone or followed by benznidazole (Bz) chemotherapy. A vaccine formulation based on an N-terminal fragment of Trans-sialidase (TS) and Immunostimulant Particle Adjuvant (ISPA) - TSNt-ISPA was obtained. Firstly, the immunogenicity and protective capacity of TSNt-ISPA was demonstrated as a prophylactic formulation in an acute model of infection. Later, the formulation was assessed as a therapeutic vaccine alone or combined with (Bz) using two models of chronic infection. BALB/c mice chronically infected with Sylvio X10/4 or Tulahuen cl2 T. cruzi strains were not treated as control or treated only with the therapeutic vaccine TSNt-ISPA, with a combined treatment TSNt-ISPA+Bz (Bz applied after the vaccine), or only with Bz. The vaccination schedule consisted of TSNt-ISPA administration at days110, 120, and 130 post-infection (pi) and Bz administration was performed daily from day 140 to 170 pi. At day 273 pi, electrocardiographic (ECG) parameters, heart parasite load, myocarditis, and heart fibrosis were assessed. In both models, therapeutic administration of TSNt-ISPA reduced ECG alterations and the cardiac tissue damage observed in the chronic phase. Moreover, vaccine treatment significantly decreased heart parasite load in both Sylvio X10/4 and Tulahuen cl2 infected mice. The combined treatment, but not Bz or vaccine administration alone, allowed to restore ECG parameters in Tulahuen cl2 infected mice. The results indicate the usefulness of the therapeutic TSNt-ISPA formulation in BALB/c mice chronically infected with Sylvio X10/4 or Tulahuen cl2 strain. For the mice infected with T. cruzi Tulahuen cl2 strain, the combined treatment with the vaccine and Bz had a more positive effect on the course of heart disease than the individual treatments with the vaccine or Bz alone.
ISSN:0001-706X
1873-6254
DOI:10.1016/j.actatropica.2022.106334