Intraspleen delivery of a DNA vaccine coding for superoxide dismutase (SOD) of Brucella abortus induces SOD-specific CD4+ and CD8+ T cells.
In the development of vaccines capable of providing immunity against brucellosis, Cu-Zn superoxide dismutase (SOD) has been demonstrated to be one of the protective immunogens of Brucella abortus. In an earlier study, we provided strong evidence that intramuscular injection with a plasmid DNA carrying the SOD gene (pcDNA-SOD) was able to induce a protective immune response. The present study was designed to characterize T-cell immune responses after an intraspleen (i.s.) vaccination of BALB/c mice with pcDNA-SOD. Animals vaccinated with pcDNA-SOD did not develop SOD-specific antibodies, at least until week 4 after immunization (the end of the experiment), and in vitro stimulation of their splenocytes with either recombinant Cu-Zn SOD or crude Brucella protein induced the secretion of gamma interferon (IFN-gamma), but not interleukin-4, and elicited the induction of cytotoxic-T-lymphocyte activity. Upon analyzing the SOD-specific T-cell responses, the pcDNA-SOD vaccination was found to be stimulating both CD4(+)- and CD8(+)-T-cell populations. However, only the CD4(+) population was able to produce IFN-gamma and only the CD8(+) population was able to induce cytotoxic activity. Nevertheless, although i.s. route vaccination induces a significant level of protection in BALB/c mice against challenge with the virulent B. abortus strain 2308, vaccination by the intramuscular route with a similar amount of plasmid DNA does not protect. Based on these results, we conclude that i.s. immunization with pcDNA-SOD vaccine efficiently induced a Th1 type of immune response and a protective response that could be related to IFN-gamma production and cytotoxic activity against infected cells by SOD-specific CD4(+) and CD8(+) T cells, respectively.
Muñoz-Montesino
Carola
C
Molecular Immunology Laboratory, Department of Microbiology, Faculty of Biological Sciences, Universidad de Concepción, Concepción, Chile.
Andrews
Edilia
E
Rivers
Rodolfo
R
González-Smith
Andrés
A
Moraga-Cid
Gustavo
G
Folch
Hugo
H
Céspedes
Sandra
S
Oñate
Angel A
AA
D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology; D002003:Brucella abortus / Q000201:enzymology / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D002006:Brucellosis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015169:Colony Count, Microbial; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000382:microbiology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
D001428:Bacterial Vaccines; D019444:Vaccines, DNA; D007371:Interferon-gamma; D013482:Superoxide Dismutase