Rational development of prophylactic HIV vaccines based on structural and regulatory proteins.

The severity of the AIDS epidemic clearly emphasises the urgent need to expedite HIV vaccine candidates into clinical trials. Prophylactic HIV vaccine candidates have been evaluated in non-human primates. Based on specific proof of principle studies the first phase III clinical studies have recently begun in humans. However, a truly effective HIV vaccine is not yet at hand and many problems related to specific properties of the virus remain to be overcome. Previously proven empirical approaches have largely failed and now rational thinking based on an understanding of immunity to lentiviral infections is needed. This review addresses the scientific problems and complications facing the development of an HIV vaccine as well as the possible strategies currently available to overcome these problems. Recent attention has focussed on identifying the immune correlates and mechanisms of protection from either HIV infection or protection from disease progression. Based on these observations, the logic and rational behind the development of multiple component vaccine strategies are highlighted.