ORAL DNA VACCINE OF AN ENGINEERED CHIMERIC IMMUNOGEN BETWEEN ATrypanosomacruziANTIGEN AND A NON-TOXIC SUPERANTIGEN DELIVERED BY ATTENUATED Salmonella INDUCES PROTECTION AGAINST T.cruzi CHALLENGE

MALCHIODI EMILIO LUIS; REDOLFI, DANIELA; FERNÁNDEZ LYNCH, JULIETA; ANTONOGLOU, BELÉN; FERNÁNDEZ MARISA MARIEL; SARRATEA, BELÉN; BIVONA, AUGUSTO; VON RÜSTEN, ISABEL; NOLI TRUANT, SOFIA; SANCHEZ ALBERTI, ANDRÉS

CABA

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Sociedad Argentina de Investigación Clínica (SAIC), Sociedad Argentina Bioquímica y Biología Molecular (SAIB), Sociedad Argentina Inmunología (SAI), Sociedad Argentina Fisiología (SAFIS), Sociedad Argentina Farmacología Experimental (SAFE), Sociedad Arge

There is still an urgent need for an effective vaccine to prevent and treat Chagas disease.Our group has developed superantigen mutants (mSAg) that lack T cell activation capability but bind MHC-II on antigen presenting cells. In this work, we engineered a chimeric antigen (chimera) between mSAg and a protective Trypanosomacruzi antigen. Our goal was to evaluate the ability of chimera-DNA immunization through a Salmonella-based delivery system to induce protection in a murine model of T.cruzi.Chimera was genetically engineered, cloned in two expression vectors: pET32 and pcDNA3.1; and was produced as a recombinant protein in E.coli.Attenuated Salmonellawas transformed with pcDNA3.1-chimera (Schimera).C3H/HeN mice were immunized with four total doses as follows: I-109Schimera (orally); II- chimera (10 µg/dose) + ODN-CpG (intramuscularly); III- two Schimera + two boosts of chimera; IV- two Schimera + two boosts of chimera + ODN-CpG; V- 109 Salmonella with empty pcDNA (control). Two weeks after the last immunization,T.cruzi antigen-specific IgG titers and IgG1/IgG2a isotypes were determined. Animals were challenged with 1000 bloodstream trypomastigotes (RA strain). Parasitemia levels were registered every two days and survival was monitored daily.Specific antibody titers against T.cruzi antigen were detected in groups II, III and IV, showing significant differences against the control group (p