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

BIVONA, AUGUSTO E; SCHULZE, KAI; GONZÁLEZ, GERMÁN; CAZORLA, SILVIA I; SANCHEZ ALBERTI, ANDRÉS; CERNY, NATACHA; EBENSEN, THOMAS; CARDOSO, ALEJANDRO C.; MALCHIODI, EMILIO L; MATOS, MARINA N; WEISSMANN, SEBASTIAN; MORALES, CELINA; GUZMAN, CARLOS A

Beijing

Congreso; 17th International Congress of Immunology; 2019

International Union Of Immunological Societies (IUIS)

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