The Quest for an AIDS Vaccine: The State of the Art and Current Challenges

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Abstract
Despite intense efforts worldwide, using state-of-the art methods and techniques and despite ever-increasing knowledge about the molecular and structural make-up of HIV, a practical vaccine against acquired immunodeficiency syndrome (AIDS) has yet to be developed. The increasing use of recombinant DNA techniques and synthetic peptide technology has allowed many groups to identify at the epitope level the regions of HIV proteins which act as targets for (and stimulate) the immune response. Epitopes which stimulate and bind neutralizing antibodies have been examined in detail and an ever-increasing number of antibody-dependent cellular cytotoxicity (ADCC) and cytotoxic T lymphocytes (CTL) epitopes are being defined, as are potentially harmful (immunosuppressive or enhancing) domains. It still is not clear which of the different immune responses (or combinations thereof) it will be necessary to stimulate in order to protect from infection. Infected humans develop neutralizing antibodies, ADCC-inducing antibodies and CTL responses against a variety of viral proteins but it is not known which of these can control or prevent infection in vivo. The extensive knowledge of HIV and the immune response it elicits is being used to design and produce a wide variety of putative vaccines, ranging from whole inactivated virus, through recombinant organisms/proteins, to synthetic peptides although each has its inherent advantages and disadvantages. The very nature of HIV makes vaccine development difficult at best. However, recent successes using whole inactivated virus or virus-infected cells in the macaque simian immunodeficiency virus (SIVmac) model system at least show that protection against lethal lentivirus infection can be achieved. The outlook for an eventual vaccine to prevent HIV infection is therefore, at the moment, an optimistic one.