Tc52 amino-terminal-domain DNA carried by attenuated Salmonella enterica serovar Typhimurium induces protection against a Trypanosoma cruzi lethal challenge.

Abstract:

:In this work we immunized mice with DNA encoding full-length Tc52 or its amino- or carboxy-terminal (N- and C-term, respectively) domain carried by attenuated Salmonella as a 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 lysis of the trypomastigotes in the presence of complement and inhibit their invasion of mammal cells in vitro. The strongest functional activity was observed with sera from mice immunized with Salmonella carrying the N-term domain (SN-term), followed by Tc52 (STc52), and the C-term domain (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 interleukin-10 (IL-10), counterbalancing the inflammatory reaction, and also strong activation of Tc52-specific gamma interferon-positive (IFN-γ(+)) CD8(+) T cells. In agreement with this, although all prototypes conferred protection against infection, immunization with SN-term promoted greater protection than that with SC-term for all parameters tested and slightly better protection than that with STc52, especially in the acute stage of infection. We conclude that the N-terminal domain of Tc52 is the section of the protein that confers maximal protection against infection and propose it as a promising candidate for vaccine development.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Matos MN,Cazorla SI,Bivona AE,Morales C,Guzmán CA,Malchiodi EL

doi

10.1128/IAI.02190-14

subject

Has Abstract

pub_date

2014-10-01 00:00:00

pages

4265-75

issue

10

eissn

0019-9567

issn

1098-5522

pii

IAI.02190-14

journal_volume

82

pub_type

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