Co-delivery of plasmid-encoded cytokines modulates the immune response to a DNA vaccine delivered byin vivoelectroporation

• Published in: Vaccine Vol. 25; no. 14; p. 2575
• Main Authors: Yen, Hung-Hsun, Scheerlinck, Jean-Pierre Y
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Limited 30.03.2007
• Subjects: Animals; Cloning; Deoxyribonucleic acid; DNA; Immune system; Plasmids; Proteins; Sheep; Studies; Vaccines
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2006.12.025

In this study,in vivoelectroporation 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 ofHaemonchus contortus(pNPA) and plasmids encoding different cytokines followed byin vivoelectroporation. Plasmids (pCI) carrying the genes of different cytokines including ovine IL-4(pCI-IL4), IL-10(pCI-IL10), GM-CSF(pCI-GMCSF), and MCP-1α(pCI-MCP1α), 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 within vivoelectroporation has the ability to effectively modulate immune responses to a DNA vaccine in a large animal.