A fusion DNA vaccine that targets antigen-presenting cells increases protection from viral challenge

Improving the immunological potency, particularly the Ab response, is a ser ious hurdle for the protective efficacy and hence broad application of DNA vaccines. We examined the immunogenicity and protective efficacy of a hemag glutinin-based influenza DNA vaccine that was targeted to antigen-presentin g cells (APCs) by fusion to CTLA4, The targeted vaccine was shown to induce an accelerated and increased Ab response (as compared with those receiving the nontargeted control) that was predominated by IgG1 and recognized conf ormationally dependent viral epitopes, Moreover, mice receiving the APC-tar geted DNA vaccine had significantly reduced viral titers (100-fold) after a nonlethal virus challenge. The increased protective efficacy was most like ly because of increased Ab responses, as cytotoxic T lymphocyte responses w ere not enhanced. Targeting was demonstrated by direct binding studies of C TLA4 fusion proteins to the cognate ligand (B7; expressed on APCs in vivo). In addition, a targeted protein was detected at 4-fold higher levels in dr aining lymph nodes within 2-24 h of administration. Therefore, this study d emonstrates that targeting DNA-encoded antigen to APCs results in enhanced immunity and strongly suggests that this approach may be useful in improvin g the protective efficacy of DNA vaccines.