DNA fusion vaccines incorporating IL-23 or RANTES for use in immunization against influenza.
The incorporation of RANTES or IL-23 into DNA vaccines may improve their immunogenicity by the recruitment and activation of dendritic cells. This may also select for a TH1 response counteracting the TH2 response which can predominate when a DNA vaccine is delivered by gene gun. We have immunized mice with various DNA constructs encoding APR/8/34 influenza virus hemagglutinin (HA), either fused to or separate from, IL-23 or RANTES using a gene gun. Those immunized with IL-23/HA fusion constructs and challenged with influenza 27 weeks post-vaccination, tended to have cleared more virus than those vaccinated with HA DNA. Mice immunized with the RANTES/HA fusion construct produced a mixed TH1/TH2 response whereas in HA-vaccinated mice, a TH2 response predominated. Immunization with a plasmid in which HA and RANTES were under the control of separate promoters, failed to generate a mixed TH1/TH2 response suggesting that enhanced antigen uptake via RANTES receptors may contribute to the mixed immune response generated to the fusion construct. Overall these findings provide further evidence that Type 1 cytokines or chemokines, fused to antigen in a DNA vaccine, can influence the nature and the longevity of the immune response and ultimately, its protective capacity.
Williman
J
J
Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
Young
S
S
Buchan
G
G
Slobbe
L
L
Wilson
M
M
Pang
P
P
Austyn
J
J
Preston
S
S
Baird
M
M
D000818:Animals; D018946:Chemokine CCL5 / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D007114:Immunization; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D053759:Interleukin-23 / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D018946:Chemokine CCL5; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D053759:Interleukin-23; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA