HIV vaccines: brief review and discussion of future directions.

A major barrier to the design of a successful HIV vaccine is virus diversity,which is particularly apparent in the envelope glycoprotein, the target of neutralizing antibodies. An antibody generated to one envelope glycoprotein may not recognize an isolate bearing a different envelope glycoprotein. Thus, single-envelope glycoprotein vaccines have protected against homologous but not necessarily against heterologous challenge. Antigenic diversity has been addressed in the design of vaccines for other pathogens by the preparation of polyvalent vaccines. The poliovirus vaccine, for example, comprises three serotypes of poliovirus, a feature that was essential in providing full protection against polio infection. Similarly, the authors propose that overcoming HIV diversity is likely to require the administration of a cocktail of envelope glycoprotein antigens. Delivery of such an array of envelope glycoproteins will elicit a broad immune response that is potentially capable of recognizing the diverse population of HIV-1 isolates. This article reviews data relevant to the development of cocktail vaccines which have been designed to elicit a wide range of envelope glycoprotein-specific B- and T-cell responses.