Tc52 Amino Terminal Domain DNA Carried by Attenuated Salmonella Induce Protection against a Trypanosoma cruzi Lethal Challenge

MATOS, MARINA NADIA; CAZORLA, SILVIA INES; BIVONA, AUGUSTO E.; MORALES, CELINA; GUZMÁN, CARLOS A.; MALCHIODI, EMILIO L.

INFECTION AND IMMUNITY

AMER SOC MICROBIOLOGY

Lugar: Washington; Año: 2014 vol. 82 p. 4265 - 4275

0019-9567

In this work we immunized mice with DNA encoding full length Tc52, or its amino- or carboxy-terminal domain (N- and C-term, respectively) carried by attenuated Salmonella as DNA delivery system. As expected, Salmonella-mediated DNA delivery resulted in low antibody titers and a predominantly Th1 response, as shown by the ratio of IgG2a/IgG1 specific antibodies. Despite modest expression of Tc52 in trypomastigotes, the antibodies elicited by vaccination were able to mediate their lysis in the presence of complement and inhibit trypomastigote invasion of mammal cells in vitro. The strongest functional activity was observed with sera from mice immunized with Salmonella carrying N-term (SN-term), followed by STc52 and SC-term. All immunized groups developed strong cellular responses with predominant activation of Th1 cells. However, mice immunized with SN-term showed higher levels of IL10, counterbalancing the inflammatory reaction, and also strong activation of Tc52-specific IFN-γ+ CD8+ T cells. In agreement with this, although all prototypes conferred protection against infection, SN-term promoted greater protection than SC-term for all parameters tested, and a slightly better edge with respect to STc52, especially in the acute stage of infection. We conclude that the N-terminal domain of Tc52 is the portion of the protein that confers maximal protection against infection, and propose it as a promising candidate for vaccine development.