THE ROLE OF ENGINEERED BACTERIAL OUTER MEMBRANE VESICLES IN CONFERRING PROTECTIVE IMMUNITY AGAINST CHAGAS DISEASE

VAZQUEZ, MARIA ELISA; ANDREA C. MESIAS; ZABALA, BRENDA ANDREA; SPANGLER, JOSEPH; PARODI, CECILIA; WALPER, SCOTT A; LEONARDO ACUÑA; CECILIA PEREZ BRANDAN

Congreso; Reunion Conjunta SAIB SAMIGE; 2020

Sociedad Argentina de Investigación Bioquímica y Biología Molecular

The limited protective immunity induced by most of the vaccine candidates evaluated so far for Chagas disease demands the development of novel strategies able to trigger a broader and longer immunity. Thanks to their potent built-in adjuvanticity, bacterial outer membrane vesicles (OMVs) represent an attractive vaccine platform for many diseases. Among their several beneficial characteristics we could mention the simplicity in their production process as well as the possibility of being genetically engineered. In this study we investigated, in a mouse model, the protective capacity of recombinant OMVs expressing different Trypanosoma cruzi antigens. Initially we would like to highlight the success in expressing, for the first time, trypanosomatid antigens in bacterial OMVs. Engineered OMVs elicited high anti-OMVs and specific antigen antibodies when administered in mice after three separately doses. The humoral phenotype obtained from serum samples was balanced between a Th1/Th2 response which is in agreement with the cytokine profile obtained in supernatant of stimulated spleen cells from vaccinated animals. At the cellular level no significant differences were found between the percentage of effector or memory CD4+ and CD8+ T cells. A robust protection was observed after challenge of immunized animals with virulent T. cruzi parasites. This work not only provides strong evidence that OMVs can be successfully decorated with T. cruzi antigens but also that mice immunized with engineered OMVs were partially protected against a virulent challenge. These results make recombinant OMVs a promising tool to be further investigated in Chagas disease vaccine approaches.