DNA immunisation: altering the cellular localisation of expressed protein and the immunisation route allows manipulation of the immune response.

DNA immunisation by intramuscular (IM) injection induces Th1 responses, whereas gene gun (GG) immunisation into the skin stimulates Th2 responses. Three ovalbumin (OVA) cDNA constructs, in which OVA is cytoplasmic (CYT), secreted (SECR), or transmembrane (TM), were compared in immunisation studies using intramuscular injection or biolistic bombardment of the skin. Gene gun immunisation with OVA-CYT or OVA-TM led to strong OVA-specific CTL responses, but not following OVA-SECR immunisation. In contrast, intramuscular immunisation with OVA-SECR or OVA-TM led to potent CTL while immunisation with OVA-CYT was ineffective. OVA-specific antibodies were detected following gene gun immunisation with all three constructs, whereas only the OVA-SECR construct induced antibody production following intramuscular immunisation. These results demonstrate the capacity to manipulate the nature of the immune response by altering the cellular localization of expressed proteins and the route of DNA immunisation.