Adenoviral vector encoding the catalytic domain of the cysteine protease Cruzipain confers immunoprotection against infection by parasite Trypanosoma cruzi.

BASTONE ANTONELLA; AUGUSTO E BIVONA; SANCHEZ ALBERTI ANDRES; NATACHA CERNY; CAZORLA SILVIA INES; ALEJANDRO C CARDOSO LANDABURU; EMILIO L MALCHIODI

Congreso; LXI Reunión Científica de la Sociedad Argentina de Biología (SAIC); LXIV Reunión Anual de la Sociedad Argentina de Inmunología (SAI) y XLVIII Reunión Anual de la Sociedad Argentina de Farmacología Experimental (SAFE).; 2016

Chagas Disease is caused by the protozoan Trypanosomacruzi and it affects about 7 million people all over the world,particularly poor people in developing countries. Available drugsfor treatment are only effective in the acute phase of the diseaseand have several adverse effects and high toxicity. The severityof the Chagas disease together with the lack of adequate chemotherapeutictreatment for the chronic infection justify the needto develop effective prophylactic and/or therapeutic vaccines.To this end, we evaluated in this work an immunization protocolusing an adenoviral vector encoding the catalytic N-terminusdomain of Cruzipain, T. cruzi?s main cysteine protease (AdNtCz),delivered by different administration routes. We also evaluatedSalmonella enterica serovar Typhimurium aroA 7207 as anotherdelivery system, encoding NtCz as well. Adenoviral vector encodingâ-galactosidase from Escherichia coli (Adâgal) was employedas control group. After being challenged with the parasite, vaccinatedmice showed reduced parasitemia (AUC control/AUCvaccinated = 3, p<0.001), increased survival rates and lowerweight loss compared to control group. Most importantly, thePrime Boost protocol (1 dose AdNtCz + 1 dose of recombinantCruzipain with CpG Oligodeoxynucleotide as adjuvant) showed100% of survival against a lethal dose of parasites (p<0.05).These results suggest that AdNtCz conferred immunoprotectionagainst infection.