DNA fusion vaccines incorporating IL-23 or RANTES for use in immunization against influenza.
Williman J., Young S., Buchan G., Slobbe L., Wilson M., Pang P., Austyn J., Preston S., Baird M.
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.