Cruzipain and Its Physiological Inhibitor, Chagasin, as a DNA-Based Therapeutic Vaccine Against Trypanosoma cruzi

CERNY, NATACHA; BIVONA, AUGUSTO ERNESTO; SANCHEZ ALBERTI, ANDRÉS; TRINITARIO, SEBASTIÁN NICOLÁS; MORALES, CELINA; CARDOSO LANDABURU, ALEJANDRO; CAZORLA, SILVIA INÉS; MALCHIODI, EMILIO LUIS

Frontiers in Immunology

Frontiers Editorial Office

Año: 2020 vol. 11

Chagas disease caused by the protozoan parasite Trypanosoma cruzi is endemic in21 Latin American countries and the southern United States and now is spreadinginto several other countries due to migration. Despite the efforts to control the vectorthroughout the Americas, currently, there are almost seven million infected peopleworldwide, causing ∼10,000 deaths per year, and 70 million people at risk to acquirethe infection. Chagas disease treatment is restricted only to two parasiticidal drugs,benznidazole and nifurtimox, which are effective during the acute and early infections buthave not been found to be as effective in chronic infection. No prophylactic or therapeuticvaccine for human use has been communicated at this moment. Here, we evaluate in amouse model a therapeutic DNA vaccine combining Cruzipain (Cz), a T. cruzi cysteineprotease that proved to be protective in several settings, and Chagasin (Chg), which is thenatural Cz inhibitor. The DNAs of both antigens, as well as a plasmid encoding GM-CSFas adjuvant, were orally administrated and delivered by an attenuated Salmonella strain totreat mice during the acute phase of T. cruzi infection. The bicomponent vaccine basedon Salmonella carrying Cz and Chg (SChg+SCz) was able to improve the protectionobtained by each antigen as monocomponent therapeutic vaccine and significantlyincreased the titers of antigen- and parasite-specific antibodies. More importantly, thebicomponent vaccine triggered a robust cellular response with interferon gamma (IFN-g)secretion that rapidly reduced the parasitemia during the acute phase and decreased thetissue damage in the chronic stage of the infection, suggesting it could be an effectivetool to ameliorate the pathology associated to Chagas disease.