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.