An effective vaccine is urgently needed to stop AIDS-epidemic. Up to now none of the candidate HIV-vaccines has been developed to prevent HIV-1 infection. A few neutralizing antibodies against HIV-1 enveloping proteins proved to be highly effective to neutralize different strains in vitro. Unfortunately, these antibodies are rare in infected humans, and have never yet been raised by a vaccine. The multiple sequential and antigenic variability of HIV-1 led to unprecedented difficulties in development of effective vaccines and anti-viral drugs. More and more experimental evidences indicated that HIV-1 mutants resulted in immune evasion may be a grave challenge for conventional strategy to prepare effective vaccines. We suggested that epitope-vaccine could be a new strategy to induce high levels of neutralizing antibodies with predefined epitope-specificity against HIV-1. Several candidate epitope-vaccines including mono-epitope-vaccine, multi-epitope-vaccine, epitope-vaccines in combination, were prepared and systematically studied in animal experiments. These studies provided experimental evidences that epitope-vaccine could be a new strategy to develop effective vaccines for prevention and immunotherapy against viral infection of HIV-l or other viruses.