Cationic influenza virosomes as an adjuvanted delivery system for CTL induction by DNA vaccination

DNA vaccines have emerged as an attractive approach to induce CTL responses against cancer and infectious agents in recent years. Although CTL induction by DNA vaccination would be a valuable strategy for controlling viral infections, increasing the potency of DNA vaccines is mandatory before DNA vaccines can make it to the clinic. In this study, we developed and characterized a new and safe adjuvanted delivery system for DNA vaccination using cationic influenza virosomes (CIV). CIV were produced by reconstitution of detergent-solubilized influenza virus membranes in the presence of cationic lipids. Plasmid DNA (pDNA) mixed with these virosomes was efficiently transfected into cells of a mouse macrophage cell line (RAW-Blue cells). Moreover, the cells were effectively activated as demonstrated by production of an NFκB/AP-1-inducible reporter enzyme. Following three intradermal immunizations, CIV-delivered epitope-encoding pDNA induced equal numbers of IFNγ- and granzyme B-producing T cells than a 10-fold higher dose of naked pDNA. Virosomes without cationic lipids also improved induction of cellular immunity by pDNA but to a significantly lower extent than CIV. These findings suggest that pDNA–CIV complexes could be an efficacious delivery system suitable for CTL induction by DNA vaccination.

► Cationic influenza virosomes efficiently transfected plasmid DNA into mouse macrophage cells. ► Cationic influenza virosomes profoundly stimulated mouse macrophage cells. ► pDNA loaded on cationic influenza virosomes induced CTL responses to an equal extent as a ten-fold higher dose of naked pDNA.