IMPAM   23988
INSTITUTO DE INVESTIGACIONES EN MICROBIOLOGIA Y PARASITOLOGIA MEDICA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Sting agonist and antigen design as a vaccine model to combat parasitic chronic infections
Autor/es:
SANCHEZ ALBERTI ANDRES; BIVONA AUGUSTO; CERNY NATACHA; CAZORLA SILVIA INÉS; CARDOSO LANDABURU ALEJANDRO; SCHULZE KAI; WEIßMANN STEFAN; GUZMAN CARLOS ; MALCHIODI EMILIO LUIS
Lugar:
Seattle
Reunión:
Simposio; Keystone Symposium. The Modes of Action of Vaccine Adjuvants (S1); 2014
Resumen:
T. cruzi is an obligatory intracellular parasite recognized by WHO as a neglected tropical disease, which affects 12 million people in Latin America. After 100 years of its discovery, there are still no effective vaccines to prevent or treat the infection. In this work we employed rational design of the immunogen based in the three dimensional structure, in order to present a multivalent display of key parasitic cytotoxic T lymphocyte (CTL) and antibody targets as well as to omit known immune evasion associated sequences. In search for novel components to increase the levels of CTL response, we have employed cyclic di nucleotides (CDNs) ? 3?5?-c-di-AMP (a STING agonist) with recombinant (r) Protein or DNA-prime + rProtein-boost ? in vaccination protocols by the intranasal route. With these strategies, we have been able to obtain not only an excellent humoral immune response that blocked in-vitro infection (60% vs. preimmune serum) but also a robust cell mediated immunity. Regarding the rProtein/c-di-AMP protocol, we determined the profile of the immune response by ELISPOT assay resulting in a balance TH1/TH17 profile for immunized groups vs controls. In addition, we observed an expansion of pathogen specific CD8 T lymphocytes comparing with the control group (%TEWETGQI+ CD8+ T cells 2.2 vs. 0.2 p