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

ANTONOGLOU, MARÍA B.; SANCHEZ ALBERTI, ANDRÉS; BIVONA, AUGUSTO E.; FERNÁNDEZ LYNCH, MARÍA J.; NOLI TRUANT, SOFÍA; SARRATEA, MARÍA B.; FERNÁNDEZ, MARISA M.; MALCHIODI, EMILIO L.

Mar del Plata

Congreso; LXIV Reunión Científica Anual de la Sociedad Argentina de Inmunología; 2016

Chagas disease 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 the infection. SEG is a bacterial superantigen (SAgs) that promotes a cytokine storm after binding MCH-II molecules and TCRs. Due to their characteristics, mutant SAgs are proposed to be used as immune modulators. In the present work we evaluated the use of SEG mutant N24A in combination with the catalytic domain of the cystein proteinase of T. cruzi, cruzipain (Nt-Cz) in vaccination protocols to analyze the immune response. SEG-N24A and Nt-Cz were cloned in bacterial plasmids, produced as recombinant proteins in E.coli and purified by Ni++/NTA column. C3H/HeN mice were 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-specific serum IgG titers were determined by indirect ELISA. In addition, delayed-type hypersensitivity (DTH) test was performed by intradermal injection of Nt-Cz in the mice footpad and swelling responses were measured 48 h later. Specific antibody titers against Nt-Cz were detected in groups III, IV and V, showing significant differences against the control group. Despite no significant differences in DTH assay, there was a stronger cellular immune reaction in the groups containing Nt-Cz compared with the control group. These results suggest that SEG-N24A is as able as ODN-CpG to induce specific IgG and DTH against a vaccine candidate as Nt-Cz. Importantly, no collateral superantigen activity was detected in mice.These preliminary studies show a potential adjuvant activity of SEG-N24A. Its use in combination with parasite antigens represents a promising tool for vaccines against T. cruzi.