Figure 7. Interpretative drawing of proposed mechanism of action of targeted versus non-targeted DNA vaccines.

Injection of DNA (1a,1b) and electroporation (2a,2b) have an adjuvant effect by inducing an inflammatory reaction in muscle resulting in elevated levels of chemokines (3). Transfected muscle cells produce (4, red colour) and secrete the targeted (5, upper) and non-targeted (5, lower) vaccine molecules. By an unknown mechanism, the targeted vaccibody induce an infiltration after >2 days predominantly composed of macrophages/DC, neutrophils and eosinophils (6). Targeted vaccibodies could drain to lymph node either unbound or bound to MHC II⁺ APC, but this remains to be determined. In contrast, non-targeted vaccibodies probably drain to lymph node as unbound molecules. In draining lymph nodes, targeted vaccibodies induce APC-B cell synapses and generation of T helper cells [25], resulting in strong stimulation of antigen specific B cells and generation of antibody secreting plasma cells (7). By contrast non-targeted vaccibodies do not induce APC-B cell synapses, and generation of T helper cells is poor [25] (8), resulting in inefficient plasma cell generation and antibody production.