title: Intramuscular immunization with a monogenic plasmid DNA tuberculosis vaccine: Enhanced immunogenicity by electroporation and co-expression of GM-CSF transgene.
abstract: Plasmid DNA vaccine has been widely explored for tuberculosis immunization but there is a need to develop the ways to improve its immunogenicity. In this study, we have constructed a plasmid DNA vaccine coding for Ag85A alone or for both Ag85A and GM-CSF and investigated the immune adjuvant effects of electroporation and GM-CSF co-expression, alone or in combination, on CD4 and CD8 T cell IFN-gamma responses, CTL activities and immune protection from pulmonary Mycobacterium tuberculosis challenge in a Balb/c mouse model. We have found that use of electroporation allows a single intramuscular (i.m.) DNA injection to be as effective as repeated i.m. DNA injections in activation of both Ag85A-specific CD4 and CD8 T cells. Co-expression of immune-enhancing cytokine GM-CSF by the same plasmid DNA TB vaccine could further enhance T cell activation including CTL activities on top of electroporation. With regard to immune protection from pulmonary M. tb challenge, use of electroporation also allows a single i.m. DNA injection to be as effective as repeated i.m. DNA injections. Co-expression of GM-CSF transgene also moderately enhances immune protection and such effect is more evident for systemic protection. However, GM-CSF expression has little added effect on immune protection by electroporation-aided immunization protocols. Our findings thus will help with the development of future DNA TB immunization strategies.
authors.affiliation: Department of Pathology and Molecular Medicine and Division of Infectious Diseases, Center for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Xizhong
authors.initials: X
authors.lastname: Zhang
authors.forename: Maziar
authors.initials: M
authors.lastname: Divangahi
authors.forename: Patricia
authors.initials: P
authors.lastname: Ngai
authors.forename: Michael
authors.initials: M
authors.lastname: Santosuosso
authors.forename: James
authors.initials: J
authors.lastname: Millar
authors.forename: Anna
authors.initials: A
authors.lastname: Zganiacz
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Jonathan
authors.initials: J
authors.lastname: Bramson
authors.forename: Zhou
authors.initials: Z
authors.lastname: Xing
mesh_terms: D000276:Adjuvants, Immunologic / Q000235:genetics*; D000818:Animals; D001500:BCG Vaccine / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002469:Cell Separation; D015169:Colony Count, Microbial; D018274:Electroporation; D005260:Female; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics* / Q000276:immunology*; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000276:immunology; D019076:Transgenes / Q000276:immunology; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D001500:BCG Vaccine; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor