HIV vaccine development: lessons from the past and promise for the future.

The global HIV epidemic continues to expand, exceeding previous predictions and causing tremendous suffering. An effective vaccine represents the best hope to curtail the HIV epidemic. The past fifteen years of HIV vaccine clinical trials have not identified an ideal HIV vaccine, but have provided many valuable lessons that contribute to the current generation of promising HIV vaccine regimens. An enhanced understanding of HIV and SIV immunopathogenesis has facilitated the design of vaccination regimens that elicit specific immune responses and effector mechanisms. Intensive investigation of recombinant gp120 subunit vaccines has revealed a previously unexpected complexity in eliciting neutralizing antibodies that are active against primary isolate viruses. The importance of CD8+ CTL responses in controlling HIV and SIV viremia has led to a series of vaccine candidates that effectively induce these responses. Proof that vaccination can prevent SIV/HIV disease has now been obtained in simian models of AIDS. A number of promising HIV vaccine regimens are currently being evaluated in human trials, and the pipeline of new vaccine vectors and combination regimens appears robust. Although challenges to the development of a safe and effective global HIV vaccine remain, the outlook for HIV vaccines in the future is bright.