Mucosal Heterologous Prime/Boost Vaccination Induces Polyfunctional Systemic Immunity, Improving Protection Against Trypanosoma cruzi

There are several unmet needs in modern immunology. Among them, vaccines against parasitic diseases and chronic infections lead. Trypanosoma cruzi, the causative agent of Chagas disease, is an excellent example of a silent parasitic invasion that affects millions of people worldwide due to its progr...

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Detalles Bibliográficos
Autores: Sanchez Alberti, Andrés, Bivona, Augusto Ernesto, Matos, Marina Nadia, Cerny, Natacha, Schulze, Kai, Weißmann, Sebastian, Ebensen, Thomas, González, Germán, Morales, Celina, Cardoso Landaburu, Alejandro Cesar, Cazorla, Silvia Ines, Guzman, Carlos A., Malchiodi, Emilio Luis
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/143193
Acceso en línea:http://hdl.handle.net/11336/143193
Access Level:acceso abierto
Palabra clave:ANTI-TRYPANOSOMA CRUZI VACCINE
CELL-MEDIATED IMMUNITY
CHAGAS DISEASE
CYCLIC-DI-AMP
NEGLECTED TROPICAL DISEASE
PRIME-BOOST VACCINE
T CELL POLYFUNCTIONALITY
TRASPAIN
https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
Descripción
Sumario:There are several unmet needs in modern immunology. Among them, vaccines against parasitic diseases and chronic infections lead. Trypanosoma cruzi, the causative agent of Chagas disease, is an excellent example of a silent parasitic invasion that affects millions of people worldwide due to its progression into the symptomatic chronic phase of infection. In search for novel vaccine candidates, we have previously introduced Traspain, an engineered trivalent immunogen that was designed to address some of the known mechanisms of T. cruzi immune evasion. Here, we analyzed its performance in different DNA prime/protein boost protocols and characterized the systemic immune response associated with diverse levels of protection. Formulations that include a STING agonist, like c-di-AMP in the boost doses, were able to prime a Th1/Th17 immune response. Moreover, comparison between them showed that vaccines that were able to prime polyfunctional cell-mediated immunity at the CD4 and CD8 compartment enhanced protection levels in the murine model. These findings contribute to a better knowledge of the desired vaccine-elicited immunity against T. cruzi and promote the definition of a vaccine correlate of protection against the infection.