title: 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.
authors: Cátedra de Inmunología and Instituto de Estudios de la Inmunidad Humoral, UBA-CONICET, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina Instituto de Microbiología y Parasitología Médica, UBA-CONICET, and Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors: Marina N
authors: MN
authors: Matos
authors: Cátedra de Inmunología and Instituto de Estudios de la Inmunidad Humoral, UBA-CONICET, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina Instituto de Microbiología y Parasitología Médica, UBA-CONICET, and Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors: Silvia I
authors: SI
authors: Cazorla
authors: Cátedra de Inmunología and Instituto de Estudios de la Inmunidad Humoral, UBA-CONICET, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina Instituto de Microbiología y Parasitología Médica, UBA-CONICET, and Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors: Augusto E
authors: AE
authors: Bivona
authors: Instituto de Fisiopatología Cardiovascular, Departamento de Patología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors: Celina
authors: C
authors: Morales
authors: Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors: Carlos A
authors: CA
authors: Guzmán
authors: Cátedra de Inmunología and Instituto de Estudios de la Inmunidad Humoral, UBA-CONICET, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina Instituto de Microbiología y Parasitología Médica, UBA-CONICET, and Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina emalchio@ffyb.uba.ar.
authors: Emilio L
authors: EL
authors: Malchiodi
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D014355:Chagas Disease / Q000276:immunology / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004337:Drug Carriers; D005260:Female; D005822:Genetic Vectors; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D012486:Salmonella typhimurium / Q000235:genetics*; D017422:Sequence Analysis, DNA; D016019:Survival Analysis; D018417:Th1 Cells / Q000276:immunology; D016896:Treatment Outcome
chemical_list: C097550:52-kDa protein, Trypanosoma cruzi; D000913:Antibodies, Protozoan; D016207:Cytokines; D004337:Drug Carriers; D007074:Immunoglobulin G; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D011994:Recombinant Proteins