Engineered trivalent immunogen adjuvanted with a STING agonist confers protection against Trypanosoma cruzi infection

SANCHEZ ALBERTI, ANDRES; BIVONA, AUGUSTO E.; CERNY, NATACHA; SCHULZE K; WEIßMANN S; EBENSEN T; MORALES, CELINA; PADILLA AM; CAZORLA SILVIA I; TARLETON RICK L; GUZMAN CARLOS A; MALCHIODI EL

NaturePJ-Vaccines

Springer Nature

Lugar: Galveston, Texas; Año: 2017 p. 1 - 12

The parasite Trypanosoma cruzi is the causative agent of Chagas disease, a potentially life-threatening infection that represents amajor health problem in Latin America. Several characteristics of this protozoan contribute to the lack of an effective vaccine,among them: its silent invasion mechanism, T. cruzi antigen redundancy and immunodominance without protection. Taking intoaccount these issues, we engineered Traspain, a chimeric antigen tailored to present a multivalent display of domains from keyparasitic molecules, combined with stimulation of the STING pathway by c-di-AMP as a novel prophylactic strategy. This formulationproved to be effective for the priming of functional humoral responses and pathogen-specific CD8+ and CD4+ T cells, compatiblewith a Th1/Th17 bias. Interestingly, vaccine effectiveness assessed across the course of infection, showed a reduction in parasiteload and chronic inflammation in different proof of concept assays. In conclusion, this approach represents a promising tool againstparasitic chronic infections.