title: Co-administration of a plasmid DNA encoding IL-15 improves long-term protection of a genetic vaccine against Trypanosoma cruzi.
abstract: BACKGROUND
  Immunization of mice with the Trypanosoma cruzi trans-sialidase (TS) gene using plasmid DNA, adenoviral vector, and CpG-adjuvanted protein delivery has proven highly immunogenic and provides protection against acute lethal challenge. However, long-term protection induced by TS DNA vaccines has not been reported. The goal of the present work was to test whether the co-administration of a plasmid encoding IL-15 (pIL-15) could improve the duration of protection achieved through genetic vaccination with plasmid encoding TS (pTS) alone.
  
  
  METHODS
  We immunized BALB/c mice with pTS in the presence or absence of pIL-15 and studied immune responses [with TS-specific IFN-γ ELISPOT, serum IgG ELISAs, intracellular cytokine staining (IFN-γ, TNF-α, and IL-2), tetramer staining, and CFSE dilution assays] and protection against lethal systemic challenge at 1 to 6 months post vaccination. Mice receiving pTS alone developed robust TS-specific IFN-γ responses and survived a lethal challenge given within the first 3 months following immunization. The addition of pIL-15 to pTS vaccination did not significantly alter T cell responses or protection during this early post-vaccination period. However, mice vaccinated with both pTS and pIL-15 challenged 6 months post-vaccination were significantly more protected against lethal T. cruzi challenges than mice vaccinated with pTS alone (P<0.05). Improved protection correlated with significantly higher numbers of TS-specific IFN-γ producing total and CD8(+) T cells detected>6 months post immunization. Also, these TS-specific T cells were better able to expand after in vitro re-stimulation.
  
  
  CONCLUSIONS
  Addition of pIL-15 during genetic vaccination greatly improved long-term T cell survival, memory T cell expansion, and long-term protection against the important human parasite, T. cruzi.
authors.affiliation: Department of Internal Medicine, Saint Louis University, Saint Louis, Missouri, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Eickhoff
authors.forename: Jose R
authors.initials: JR
authors.lastname: Vasconcelos
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Sullivan
authors.forename: Azra
authors.initials: A
authors.lastname: Blazevic
authors.forename: Oscar
authors.initials: O
authors.lastname: Bruna-Romero
authors.forename: Mauricio M
authors.initials: MM
authors.lastname: Rodrigues
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hoft
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D014355:Chagas Disease / Q000276:immunology / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology*; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009439:Neuraminidase / Q000235:genetics / Q000276:immunology*; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage; D010957:Plasmids / Q000008:administration & dosage; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; C408982:CPG-oligonucleotide; D016207:Cytokines; D006023:Glycoproteins; D019409:Interleukin-15; D009838:Oligodeoxyribonucleotides; D016052:Protozoan Vaccines; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; C069715:trans-sialidase; D009439:Neuraminidase