IMMUNOGENICITY AND PROTECTIVE EFFICACY OF ANTI-T. CRUZI NASAL VACCINE PROTOTYPES BASED ON TRANSIALIDASE

ESDRAS DA SILVA OLIVEIRA BARBOSA, EDUARDO ROGGERO, ROCÍO DV FERNÁNDEZ, FLORENCIA BELÉN GONZALEZ, OSCAR BOTTASSO, ANA ROSA PÉREZ, SILVINA RAQUEL VILLAR

Mar del Plata

Congreso; Reunión SAIC-SAI-SAFIS. Mar del Plata 14 al 17 de noviembre 2018; 2018

Currently there is not available aprophylactic vaccine for Chagasdisease. Therefore, in this work weevaluated whether the administrationof different nasal vaccine prototypes couldprevent the developmentof T. cruzi (Tc) infection through theinduction of specific andsystemic immune response. A fragment fromthe immunodominantparasite antigen called transialidase (TSf),containing both B andT epitopes was selected by bioinformatics.TSf was expressed ina L. lactis recombinant strain and thenpurified, avoiding the presenceof endotoxins like LPS in vaccineformulations. Thus, femaleBalb/c mice (n= 5-6/group) were immunized byintranasal route(three doses, one every two weeks) withdifferent vaccine formulationscombining TSf with different adjuvants(c-di-AMP or ISPA).We also assayed the whole recombinant L.lactis expressing TSf asdelivery system plus c-di-AMP(LL-TSf+c-di-AMP). Non immunizedmice were used as control group (Co). Inimmunized mice, humoraland cellular immune responses were assayedprior to infection. Afteroral infection with 2500 Tc/mice (Tulahuenstrain), the parasitemiaand the clinical score were determined.Intranasal immunized micewith TSf+c-di-AMP showed enhanced levels ofIgG2a and IgG1compared to TSf and Co groups (in all cases,p<0.05). TSf+ISPAand LL-TSf+c-di-AMP immunized mice also tendto increase bothTSf-specific-antibodies compared to Co andTSf. TSf+c-di-AMP immunizedmice and, in a lesser extent TSf+ISPA,elicited a higherTS-specific cellular mediated immuneresponse after 24 and 48 h(DHT in footpads). Parasite load after 14and 28 days post-infectionwas less evident in TSf+c-di-AMP animalscompared with the restof the groups. Moreover, TSf+c-di-AMPanimals exhibited less clinicalaffectation (clinical global score,p<0.05 vs. all groups). Takentogether, these results indicate thatTSf+c-di-AMP and TSf+ISPAformulations tested in this work would be goodcandidates for thedevelopment of a prophylactic mucosal vaccine against T. cruzi.