With support from two successive, framework V, EU sponsored consortia, we have developed an in vivo targeting approach for dendritic cells (DC) applicable to protein vaccines, DNA vaccines, and viral vector vaccines. Antibodies directed against the DC-spec ific, endocytic receptor DEC-205 allowed efficient uptake and presentation of antigens coupled to the antibodies by the targeted DCs. Providing a costimulatory signal resulted in potent antiviral immune responses. Given the urgent need for an HIV vaccine, the potential of this innovative vaccine approach should be evaluated as quickly as possible. Therefore, the aims of the current application of the consortium are to determine the efficacy of DEC-205-targeted protein-, DNA-, and viral vector vaccines in an imal models and to understand requirements for and mechanisms of protection.