The use of Th1 cytokines, IL-12 and IL-23, to modulate the immune response raised to a DNA vaccine delivered by gene gun.
Unlike intramuscular injection, gene gun delivery of DNA drives a strong type 2 response. In an effort to counter this, we have genetically fused the type 1 cytokines, IL-12 and IL-23, to the hemagglutinin (HA) gene from influenza APR/8/34, and delivered these DNA constructs to Balb/c mice. Gene gun delivery of the HA gene was able to induce antibody production by all vaccinated mice. Linking of IL-12 caused almost complete suppression of immune responses whereas mice vaccinated with IL-23HA showed long-lived IgG1 antibody levels. Splenocytes from IL-23HA vaccinated mice also tended to produce more IL-5 and IFNgamma after restimulation in vitro than splenocytes from HA vaccinated mice. While codelivery of IL-23 did not change the type of immune response it may increase its longevity following vaccination.
Williman
Jonathan
J
Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, New Zealand.
Lockhart
Euan
E
Slobbe
Lynn
L
Buchan
Glenn
G
Baird
Margaret
M
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D001483:Base Sequence; D019470:Biolistics; D002460:Cell Line; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology*; D053759:Interleukin-23 / Q000276:immunology*; D051379:Mice; D009975:Orthomyxoviridae / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
D000914:Antibodies, Viral; D017931:DNA Primers; D053759:Interleukin-23; D019444:Vaccines, DNA; D018664:Interleukin-12