Mucosal heterologous prime/boost vaccination strategy induces polyfunctional systemic immunity improving protection against Trypanosoma cruzi

SANCHEZ ALBERTI ANDRES; AUGUSTO E BIVONA; CERNY, NATACHA; TRINITARIO, SEBASTIÁN N.; ALEJANDRO C CARDOSO LANDABURU; GONZÁLEZ, GERMÁN; CELINA MORALES; SCHULZE, KAI; SEBASTIAN WEIßMANN; EBENSEN, THOMAS; CAZORLA SILVIA INES; GUZMÁN, CARLOS A.; MALCHIODI EMILIO LUIS

Congreso; International Congress of Immunology, (IUIS); 2019

Chagas disease is a potentially life-threatening disease caused by the protozoanparasite Trypanosoma cruzi, that is recognized by WHO as a NTD in Latin America.Despite several efforts, there is no approved vaccine against Chagas disease. Wehave previously introduced Traspain, a chimeric antigen rationally designed to displayB/T cell epitopes of key parasitic proteins: Cruzipain, ASP-2 and Transialidase.Traspain proved to be immunogenic and protective against T. cruzi murine infection ina protein-subunit vaccine model. Here we analyzed immunogenicity and efficacy of amucosal prime/boost protocol using attenuated Salmonella as Traspain-DNA-deliverysystem, followed by boosts of rTraspain adjuvanted with cyclic-di-AMP (CDA) or CpG-ODN. In agreement with previous results, mice that received Traspain/CDA displayed aTh1/Th17 bias. However, the single Cruzipain and ASP2 combined, failed to achievesimilar levels of vaccine potency despite receiving CDA. Traspain/ODN-CpG boostshowed a Th1 profile. Traspain/CDA immunized mice showed the more equilibratedimmune response during the acute phase that correlated with a reduction of circulatingparasites and increase in survival rates upon a lethal T. cruzi challenge. We found asimilar scenario in a chronic infection models, when Traspain/CDA boost produced thestrongest reduction of blood parasites and body weight losses compared with non-vaccinated control. We concluded: CDA outperformed another adjuvant in mucosalprime/boost strategy inducing a Th17 immune response; the chimeric Traspain improvethe magnitude of the immune response compared with the single antigens combined;and the increase of polyfunctionality of cell immunity is associated with betterprotection as anti-T. cruzi vaccine.