Herein, we describe the Epimmune approach to prophylaxis and development of a multi-epitope vaccine for immunotherapy of HIV-1 infection. The central strategy of our program is to induce cellular immune responses, cytotoxic T-lymphocytes (CTL) and helper Tlymphocytes (HTL), specific for conserved epitopes from both structural and regulatory proteins of HIV-1. The HIV-1 derived and HLA-restricted CTL and HTL epitopes needed to design and construct the experimental vaccines are now known and allow for broad and non-ethnically biased coverage of the human population. The design optimization of an epitope-based DNA vaccine and evaluating methods for various DNA vaccine delivery technologies for possible use in clinical trials are addressed.