Use of a staphylococcal superantigen as a tool in a novel vaccine design against Trypanosoma cruzi infection

SANCHEZ ALBERTI ANDRES; NOLI TRUANT S; EMILIO L. MALCHIODI; AUGUSTO E BIVONA; ANTONOGLOU MB; SARRATEA MB; FERNANDEZ LYNCH MJ; FERNANDEZ M

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

Chagasdisease is a neglected infection caused by Trypanosoma cruzi which affects millions of people worldwide.Despite several efforts, there is still no vaccine to treat or prevent theinfection.  SEG isa bacterial superantigen (SAgs) that promotes a cytokine storm after bindingMCH-II molecules and TCRs. Due to their characteristics, mutant SAgs areproposed to be used as immune modulators.  In the present work we evaluated the use of SEGmutant N24A in combination with the catalytic domain of the cystein proteinase ofT. cruzi, cruzipain (Nt-Cz) invaccination protocols to analyze the immune response. SEG-N24A and Nt-Cz were cloned inbacterial plasmids, produced as recombinant proteins in E.coli and purified by Ni++/NTA column. C3H/HeN micewere subcutaneously immunized with five doses of 10 µg of total protein as follows:I-PBS; II- N24A; III-Nt-Cz with CpG-ODN as adjuvant; IV- N24A and Nt-Cz; V-N24A and Nt-Cz with CpG-ODN. Seven days after the last immunization, Nt-Cz-specificserum IgG titers were determined by indirect ELISA. In addition, delayed-typehypersensitivity (DTH) test was performed by intradermal injection of Nt-Cz inthe mice footpad and swelling responses were measured 48 h later. Specific antibody titers against Nt-Cz weredetected in groups III, IV and V, showing significant differences against thecontrol group. Despite no significant differences in DTH assay, there was a strongercellular immune reaction in the groups containing Nt-Cz compared with thecontrol group. These results suggest that SEG-N24A is as able as ODN-CpG toinduce specific IgG and DTH against a vaccine candidate as Nt-Cz. Importantly,no collateral superantigen activity was detected in mice.These preliminary studies show apotential adjuvant activity of SEG-N24A. Its use in combination with parasiteantigens represents a promising tool for vaccines against T. cruzi.