Oral DNA vaccine of an engineered chimeric immunogen between a T. cruzi antigen and a non-toxic superantigen delivered by attenuated Salmonella induces protection against T.cruzi challenge

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

Congreso; Congreso Sociedad Argentina de Inmunologia; 2017

Sociedad Argentina de Inmunologia

Abstract: There is still an urgent need for an effective vaccine to prevent andtreat Chagas disease.Our group has developed superantigen mutants (mSAg) that lack T cellactivation capability but bind MHC-II on antigen presenting cells.In this work, we engineered a chimeric antigen (chimera) between mSAg and aprotective Trypanosoma cruzi antigen. Our goal was to evaluate the ability ofchimera-DNA immunization through a Salmonella-based delivery system toinduce protection in a murine model of T.cruzi.Chimera was genetically engineered, cloned in two expression vectors: pET32and pcDNA3.1; and was produced as a recombinant protein in E.coli.Attenuated Salmonella was transformed with pcDNA3.1-chimera (Schimera).C3H/HeN mice were immunized with four total doses as follows: I- 10 9 Schimera(orally); II- chimera (10 µg/dose) + ODN-CpG (intramuscularly); III- twoSchimera + two boosts of chimera; IV- two Schimera + two boosts of chimera +ODN-CpG; V- 10 9 Salmonella with empty pcDNA (control). Two weeks after thelast immunization, T.cruzi antigen-specific IgG titers and IgG1/IgG2a isotypeswere determined. Animals were challenged with 1000 bloodstreamtrypomastigotes (RA strain). Parasitemia levels were registered every two daysand survival was monitored daily.Specific antibody titers against T.cruzi antigen were detected in groups II, IIIand IV, showing significant differences against the control group (p<0.01). Inthese groups, IgG2a titers were significantly higher than IgG1. In groups I, IIand IV parasitemia levels were low until 23 dpi, showing significant differencesagainst the control group at the peak of parasite loads (14 dpi; p<0.05). Survivalof groups I, II, III and IV was of 100% until 100 dpi.Our results indicate that immunization with this DNA-delivery system induces anefficient immune response that provides protection against T.cruzi challenge.Engineered chimeric immunogens represent useful and promising strategiesagainst parasitic chronic infections.