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.
Vaccine. 2008 Sep 19;26(40):5153-8. Epub 2008 Apr 18.

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.

URL: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TD4-4S9NDTG-1&_user=10&_coverDate=09%2F19%2F2008&_rdoc=1&_fmt=high&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=c78f174c9539503c1174473252ecec37

Pub Med: http://www.ncbi.nlm.nih.gov/pubmed/18456374

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