title: Evaluation of Brucella abortus DNA vaccine by expression of Cu-Zn superoxide dismutase antigen fused to IL-2.
abstract: The Cu-Zn superoxide dismutase (SOD) antigen of Brucella abortus was previously identified to be a T cell antigen which induces both proliferation of and gamma interferon (IFN-gamma) secretion by T cells from infected mice. In an earlier study, we demonstrated that intramuscular injection of mice with a plasmid DNA carrying the gene for SOD leads to the development of significant protection against B. abortus challenge. It has been reported that the antigen-specific immune responses generated by a DNA vaccine can be enhanced by co-delivery of certain cytokine genes. In this study, we evaluated the effect of delivering IL-2 on the efficacy of SOD DNA vaccine by generating a plasmid (pSecTag-SOD-IL2) that codes for a secretory fusion protein of SOD and IL-2. Another plasmid (pSecTag-SOD) that codes for only SOD as a secretory protein was used for comparison. BALB/c mice injected intramuscularly with pSecTag-SOD or pSecTag-SOD-IL2, but not the control plasmid pSecTag, developed SOD-specific antibody and T cell immune responses. Upon in vitro stimulation with recombinant SOD (rSOD) antigen, T cells from mice immunized with pSecTag-SOD-IL2, in comparison with those from mice immunized with pSecTag-SOD, exhibited a lower proliferation response but produced significantly higher concentrations of IFN-gamma. Both DNA vaccines, however, induced similar levels of SOD-specific antibodies and cytotoxic T cell response. Although mice immunized with pSecTag-SOD-IL2 showed increased resistance to challenge with B. abortus virulent strain 2308, this increase was not statistically significant from that of pSecTag-SOD vaccinated mice. These results suggest that a SOD DNA vaccine fused to IL2 did not improve protection efficacy.
authors.affiliation: Faculty of Biological Sciences, Molecular Immunology Laboratory, Department of Microbiology, Universidad de Concepción, P.O. Box 152-C, Concepción, Chile.
authors.forename: Andrés
authors.initials: A
authors.lastname: González-Smith
authors.forename: Ramesh
authors.initials: R
authors.lastname: Vemulapalli
authors.forename: Edilia
authors.initials: E
authors.lastname: Andrews
authors.forename: Angel
authors.initials: A
authors.lastname: Oñate
mesh_terms: D000818:Animals; D000941:Antigens / Q000096:biosynthesis / Q000235:genetics*; D002004:Brucella Vaccine / Q000235:genetics* / Q000276:immunology*; D002003:Brucella abortus / Q000276:immunology*; D002006:Brucellosis / Q000201:enzymology / Q000276:immunology / Q000517:prevention & control*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D005260:Female; D007376:Interleukin-2 / Q000008:administration & dosage / Q000235:genetics*; D051379:Mice; D011897:Random Allocation; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000941:Antigens; D002004:Brucella Vaccine; D007376:Interleukin-2; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D013482:Superoxide Dismutase