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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.

Original publication

DOI

10.1016/j.vaccine.2008.03.084

Type

Journal article

Journal

Vaccine

Publication Date

19/09/2008

Volume

26

Pages

5153 - 5158

Keywords

Animals, Chemokine CCL5, Female, Hemagglutinin Glycoproteins, Influenza Virus, Immunization, Influenza A virus, Influenza Vaccines, Interleukin-23, Mice, Mice, Inbred BALB C, Orthomyxoviridae Infections, Recombinant Fusion Proteins, Specific Pathogen-Free Organisms, Th1 Cells, Th2 Cells, Vaccines, DNA