Co-delivery of plasmid-encoded cytokines modulates the immune response to a DNA vaccine delivered by in vivo electroporation.
In this study, in vivo electroporation of a DNA vaccine adjuvanted with plasmids encoding different cytokines was investigated in large animals. Sheep were injected intramuscularly with a DNA vaccine encoding an antigen of Haemonchus contortus (pNPA) and plasmids encoding different cytokines followed by in vivo electroporation. Plasmids (pCI) carrying the genes of different cytokines including ovine IL-4(pCI-IL4), IL-10(pCI-IL10), GM-CSF(pCI-GMCSF), and MCP-1alpha(pCI-MCP1alpha), and pCI-IL4+pCI-GMCSF were co-delivered with pNPA. The results showed that co-delivery of pCI-GMCSF or pCI-IL4+pCI-GMCSF significantly enhanced both antibody responses and T cell proliferation responses to the antigen after two DNA immunisations compared to co-delivery of pCI. In contrast, antibody responses of the sheep that received pCI-IL10 were decreased significantly. Other cytokine expressing plasmids did not significantly alter the measured immune responses. Furthermore, co-delivery of pCI-GMCSF increased IgG2 response more than IgG1 responses, suggesting a Th1 bias. However, the increase in IgG2 over IgG1 was less apparent when co-delivery of pCI-IL4 with pCI-GMCSF. Interestingly, the co-delivery of pCI-IL4 alone did not increase the IgG1 titre, suggesting that both pCI-GMCSF and pCI-IL4 are required for optimal IgG1 production. Thus, co-delivery of plasmid-encoded cytokine genes with in vivo electroporation has the ability to effectively modulate immune responses to a DNA vaccine in a large animal.
Yen
Hung-Hsun
HH
Centre for Animal Biotechnology, Faculty of Veterinary Science, University of Melbourne, Vic. 3010, Australia.
Scheerlinck
Jean-Pierre Y
JP
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D018274:Electroporation; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D018073:Haemophilus Vaccines / Q000008:administration & dosage* / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D007132:Immunoglobulin Isotypes / Q000097:blood; D015847:Interleukin-4 / Q000235:genetics*; D008213:Lymphocyte Activation; D010957:Plasmids; D012756:Sheep; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology
D000907:Antibodies, Bacterial; D018073:Haemophilus Vaccines; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D019444:Vaccines, DNA; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor