Coadministration of an Interleukin-12 Gene and aTrypanosoma cruziGene Improves Vaccine Efficacy

Open Access
Publisher Website
Google Scholar
Abstract
We tested the immunogenicity of twoTrypanosoma cruziantigens injected into mice in the form of DNA vaccine. Immunization with DNA encoding dihydroorotate dehydrogenase did not confer protective immunity in all mouse strains tested. Immunization with DNA encoding trans-sialidase surface antigen (TSSA) protected C57BL/6 (H-2b) mice but not BALB/c (H-2d) or C3H/Hej (H-2k) mice against lethalT. cruziinfection. In vivo depletion of CD4+or CD8+T cells abolished the protective immunity elicited by TSSA gene in C57BL/6 mice. Enzyme-linked immunospot assay with splenocytes fromT. cruzi-infected mice or TSSA gene-vaccinated mice identified anH-2Kb-restricted antigenic peptide, ANYNFTLV. The CD8+-T-cell line specific for this peptide could recognizeT. cruzi-infected cells in vitro and could protect naive mice from lethal infection when adoptively transferred. Coadministration of the interleukin-12 (IL-12) gene with the TSSA gene facilitated the induction of ANYNFTLV-specific CD8+T cells and improved the vaccine efficacy against lethalT. cruziinfection. These results reinforced the utility of immunomodulatory adjuvants such as IL-12 gene for eliciting protective immunity against intracellular parasites by DNA vaccination.