The paper by Nchinda et al(1) asks “..whether targeting vaccine antigens to DCs would increase the immunity and protection that results from DNA vaccines”. By using scFvDEC205-antigen fusion DNA constructs delivered i.m. with electroporation, the authors clearly demonstrate this to be the case. The authors acknowledge that a number of investigators have previously demonstrated an increased efficiency of DNA vaccines that, as proteins, target molecules commonly expressed on antigen presenting cells. They go on to state that these previous reports “… have yet to prove that enhanced presentation of vaccine antigens by DC is being achieved…”. Establishment of this mechanism is the main focus of the paper. However, this mechanism has been amply demonstrated earlier. Thus, an MHC class II-specific scFv- tumor antigen DNA construct delivered i.m. with electroporation was shown to enhance priming of antigen presenting cells in draining lymph nodes, resulting in activation and proliferation of antigen-specific CD4⁺ T cells and protection against a tumor challenge(2). Targeting was shown to be essential. Similar results were obtained by using a scFv from an agonistic anti-CD40 mAb(3) and CCL3 chemokine(4) as targeting units. Bivalency and inclusion of foreign sequences increased the efficiency of targeted vaccine proteins (4). Although CD11c⁺ DC appear to be crucial for the enhanced efficiency of targeted DNA vaccines(1), future studies should further delineate the phenotypic characteristics of relevant antigen presenting cells, and what surface molecules that may be the best targets for induction of the various arms of immunity. It should also be established whether antigen presenting cells are primed with targeted vaccine proteins in muscle or in draining lymph nodes. Targeted recombinant Ig-based vaccines, pioneered in the 1990s, clearly enhance DNA immunization and are likely to yield new and more efficient vaccines for infectious diseases and perhaps also for cancer.

Reference List

1. Nchinda,G., Kuroiwa,J., Oks,M., Trumpfheller,C., Park,C.G., Huang,Y., Hannaman,D., Schlesinger,S.J., Mizenina,O., Nussenzweig,M.C. et al 2008. The efficacy of DNA vaccination is enhanced in mice by targeting the encoded protein to dendritic cells J Clin. Invest.

2. Fredriksen,A.B., Sandlie,I., and Bogen,B. 2006. DNA vaccines increase immunogenicity of idiotypic tumor antigen by targeting novel fusion proteins to antigen-presenting cells Mol. Ther. 13:776-785.

3. Schjetne,K.W., Fredriksen,A.B., and Bogen,B. 2007. Delivery of antigen to CD40 induces protective immune responses against tumors J Immunol 178:4169-4176.

4. Fredriksen,A.B., and Bogen,B. 2007. Chemokine-idiotype fusion DNA vaccines are potentiated by bivalency and xenogeneic sequences. Blood 110:1797-1805.