Human immunodeficiency virus.

A successful AIDS vaccine must elicit an immune state that will prevent the establishment of an HIV-1 persistent infection. This is a unique and difficult goal for a vaccine. Most vaccines elicit or prime for immune responses that prevent or attenuate the expression of clinical disease following infection with the pathogen. However, current evidence suggest that, following persistent infection with HIV-1, antiviral immune responses do not prevent the long-term progression to disease. Hence, it seems that the development of the persistent infection must be prevented. The ability of the immune response to accomplish this goal depends upon the efficiency with which the virus establishes persistence in the host. This is unknown for HIV-1. As a result, early efforts at vaccine development have focused on humoral immune responses directed against the virus particle in the attempt to prevent any infection of the host's cells. Studies with chimpanzees, as a model for HIV-1 infection, suggest that virus-neutralizing antibodies directed against the third hypervariable (V3) domain of the viral gp120 envelope glycoprotein may be particularly effective in preventing this infection. Studies also are in progress, both in chimpanzees and humans, to define the immunogenicity and effectiveness of various immunogens derived from the viral envelope and core structural proteins. Efforts that have concentrated on the gp120 V3 domain (or PND) have defined the extent of this region's variability and have established elements of generally conserved structure and sequence. The construction of these elements into practical and effective immunogens is an important goal. Finally, it is essential that basic studies be performed to determine if humoral or cellular immune responses directed against virus-infected cells would aid in preventing the establishment of an HIV-1 persistent infection. Such immune responses, if effective and in conjunction with specific virus-neutralizing antibody responses, would enhance the probability that an effective HIV-1 vaccine could be developed.