MUCOSAL HETEROLOGOUS PRIME-BOOST VACCINATION GENERATES SYSTEMIC IMMUNITY AND PROTECTS AGAINST A HUMAN PROTOZOAN PARASITE

SANCHEZ ALBERTI ANDRES; AUGUSTO E BIVONA; CERNY, NATACHA; TRINITARIO, SEBASTIÁN N.; ALEJANDRO C CARDOSO LANDABURU; CAZORLA SILVIA INES; CELINA MORALES; GONZÁLEZ, GERMÁN; CARLOS A. GUZMÁN; EMILIO L MALCHIODI

Congreso; IV International Congress in Treanslational Medicine - IMBS; 2018

Chagas Disease, is a potentially life-threatening illness cause by the protozoan parasiteTrypanosoma cruzi. It is recognized by WHO as a neglected tropical disease, which affects 12million people in Latin America. After 100 years of its discovery, no effective vaccine to prevent ortreat the infection is approved.We have recently introduced Traspain, a recombinant (rec) trivalent antigen rationally designedbased on the structural signature and immunological properties of each component.Here, we employed Traspain or its components in a series of mucosal DNA-prime ? recProteinboost protocols where DNA was delivered orally by attenuated Salmonella and boost doses wereperformed with a intranasal subunit vaccine strategy formulated with either ODN-CpG or c-di-AMP(CDA) as adjuvant.Results indicate that administration of CDA resulted in a more balanced and potent immuneresponse compared to CpG as was evidenced by higher frequency of diverse antigen specificcytokine secreting cells by ELISPOT. Moreover, antigen combination impacted directly in therobustness of the immune response triggered.Vaccine effectiveness assessed with lethal and sub-lethal challenge showed a reduction in parasiteload and chronic inflammation that was particularly significant for the formulation carrying traspaingene plus CDA boost. Detailed analysis of the T cell response by flow cytometry specificallycompared between Ttraspain and antigen combination group showed that higher levels of antigenspecific CD8 and CD4 T cell functionality were observed in Ttraspain group and were associatedwith a better experimental outcome in vaccinated animals. These results indicate that vaccineformulations that maximize T cell functionality as Salmonella carrying Traspain gene boosted withCDA might represent an ideal strategy for the design of effective anti-T. cruzi vaccines.