The prospects for and pathways toward a vaccine for AIDS.

This article reviews prospects for a vaccine for acquired immunodeficiency syndrome (AIDS), considered the only certain barrier to further spread of the disease. The development of an effective vaccine against another retrovirus, feline leukemia virus, suggests the possibility that a retrovirus vaccine for humans might work. However, vaccine production depends on the ability to manufacture large quantities of a safe antigen that stimulates protective immunity when it is injected into humans. There are also many nonscientific problems that must be solved, including the reluctance of the private sector to invest in such a project. If it is found that the genetic variation of human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) is limited and predictable, vaccine-induced antibodies directed toward its structural proteins, especially envelope proteins, could protect against subsequent infection. Because retroviruses have a predilection for recombination and have been associated with malignant diseases, a live attenuated retrovirus vaccine is unlikely. A killed-virus vaccine should be more acceptable, but there are problems with selecting a cell line for producing the virus, choosing methods for purifying the viral antigens, and freeing them from viral nucleic acid. Cells derived from human tumors may be necessary to support the large-scale production of immunogenic antigens. Perhaps the best option at present is recombinant DNA technology. The advantage of antigen-production systems is that the infective virus cannot be produced because only a small portion of the viral genome is incorporated. Decisions must be made about which recombinant system to use (bacterial, yeast, or mammalian cells) and which antigen or antigens should be incorporated into the vaccine. Once expressed envelope proteins are available in adequate quantity and purity for testing, an evaluation pathway that will document safety and efficacy while minimizing the time for approval needs to be established.