Genetic Immunization Elicits Antigen-Specific Protective Immune Responses and Decreases Disease Severity inTrypanosoma cruziInfection

Abstract

Immunity to Trypanosoma cruzi requires elicitation of humoral and cell-mediated immune responses to extracellular trypomastigotes and intracellular amastigotes. In this study, the effectiveness of the T. cruzi trans-sialidase family (ts) genes ASP-1, ASP-2, and TSA-1 as genetic vaccines was assessed. Immunization of mice with plasmids encoding ASP-1, ASP-2, or TSA-1 elicited poor antigen-specific cytotoxic-T-lymphocyte (CTL) activity and T. cruzi-specific antibody responses. Codelivery of interleukin-12 and granulocyte-macrophage colony-stimulating factor plasmids with antigen-encoding plasmids resulted in a substantial increase in CTL activity and antibody production and in increased resistance to T. cruzi infection. In pooled results from two to four experiments, 30 to 60% of mice immunized with antigen-encoding plasmids and 60 to 80% of mice immunized with antigen-encoding plasmids plus cytokine adjuvants survived a lethal challenge with T. cruzi. In comparison, 90% of control mice injected with empty plasmid DNA died during the acute phase of infection. However, the pool of three ts genes provided no greater protection than the most effective single gene (ASP-2) either with or without coadministration of cytokine plasmids. Importantly, the extent of tissue parasitism, inflammation, and associated tissue damage in skeletal muscles during the chronic phase of T. cruzi infection in mice immunized with antigen-encoding plasmids plus cytokine adjuvants was remarkably reduced compared to mice immunized with only cytokine adjuvants or empty plasmid DNA. These results identify new vaccine candidates and establish some of the methodologies that might be needed to develop effective vaccine-mediated control of T. cruzi infection. In addition, this work provides the first evidence that prophylactic genetic immunization can prevent the development of Chagas' disease.

Swimming against the current: genetic vaccination against Trypanosoma cruzi infection in mice

“…To determine the role of immunisation in reducing chronic phase disease symptoms, a number of experiments using different animal models must be performed. In many of the models described above, tissue inflammation and parasitism in the late chronic phase were significantly reduced following prophylactic vaccination (Garg & Tarleton 2002, Vasconcelos et al 2004, Araújo et al 2005. Therefore it is possible that prophylactic vaccinations indeed halt the development of the chronic phase immunopathologies.…”

Importance of CD8 T cell-mediated immune response during intracellular parasitic infections and its implications for the development of effective vaccines

“…They demonstrated that the genes encoding ASP-1, ASP-2 and LYT1 could provide a high degree of protective immunity against experimental infection Tarleton 2002 andFralish andTarleton 2003).…”

DNA Immunization with Na + -K + ATPase ( Sseat-6 ) Induces Protective Immunity to Larval Strongyloides stercoralis in Mice

“…An alternative vaccination approach has been to immunize mice with DNA, where the protein product is produced in vivo from the plasmid DNA. This approach has been used successfully against both protozoan (7,16,29) and helminth (10,46,53,54) infections resulting in measurable immune responses, some of which mediate protective immunity.…”