To design vaccines for viruses such as HIV that do not elicit sufficient protective immunity, we first constructed cluster vaccines containing T helper, CTL and neutralizing antibody epitopes. For second generation vaccines, we increased responses by enhancing binding to Major Histocompatibility molecules or by incorporating cytokines. We found that high avidity CTL induce better viral clearance. We also induced anti-HIV mucosal T cell immunity by intrarectal administration. Such approaches may improve classic attenuated or killed pathogen vaccines.