ABSTRACT
The limitations of current antiretroviral drug therapy have underscored the need to develop effective vaccines against human immunodeficiency virus (HIV) infection in an effort to limit the spread of acquired immunodeficiency syndrome (AIDS) worldwide. Typically, naturally occurring, protective immune responses provide the paradigm for such vaccine development; however, evidence that the immune system can provide protection against HIV infection is limited. Selected individuals exposed to HIV develop an immune response against the virus and apparently clear the infection, and some long-term nonprogressors display antiviral immune responses that presumably delay disease. Animal models have also shown limited efficacy in vaccine studies. Live-attenuated virus vaccines in the simian immunodeficiency virus (SIV) model have proven successful, but safety concerns presently limit their utility. A number of problems must therefore be solved to develop a highly effective AIDS vaccine. The identification of immunogens that elicit broadly neutralizing antibodies, an understanding of the molecular and cellular basis for immune responses to HIV components, the appropriate
forms of viral proteins for antigen presentation, stimulation of relevant T-cell types, and enhancement of antigen-presenting, dendritic cell function require further study. A high priority for vaccine development will be the establishment of methods for the systematic quantitation of immune responses in animals and in humans, as well as expanded evaluation of candidate vaccines for testing in clinical trials.
