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Engineered trivalent immunogen adjuvanted with a STING agonist confers protection against Trypanosoma cruzi infection.
Sanchez Alberti, Andrés Bivona, Augusto E Cerny, Natacha Weißmann, Sebastian Ebensen, Thomas Morales, Celina Padilla, Angel M Cazorla, Silvia I Tarleton, Rick L
Sanchez Alberti, Andrés
Bivona, Augusto E
Cerny, Natacha
Weißmann, Sebastian
Ebensen, Thomas
Morales, Celina
Padilla, Angel M
Cazorla, Silvia I
Tarleton, Rick L
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Abstract
The parasite Trypanosoma cruzi is the causative agent of Chagas disease, a potentially life-threatening infection that represents a major 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 into account these issues, we engineered Traspain, a chimeric antigen tailored to present a multivalent display of domains from key parasitic molecules, combined with stimulation of the STING pathway by c-di-AMP as a novel prophylactic strategy. This formulation proved to be effective for the priming of functional humoral responses and pathogen-specific CD8+ and CD4+ T cells, compatible with a Th1/Th17 bias. Interestingly, vaccine effectiveness assessed across the course of infection, showed a reduction in parasite load and chronic inflammation in different proof of concept assays. In conclusion, this approach represents a promising tool against parasitic chronic infections.
Citation
Engineered trivalent immunogen adjuvanted with a STING agonist confers protection against Trypanosoma cruzi infection. 2017, 2:9 NPJ Vaccines
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Language
en
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Series/Report no.
ISSN
2059-0105