Human immunodeficiency virus: scientific challenges impeding candidate vaccines.

Most initial work with HIV vaccines was directed at developing vaccines that elicited neutralizing antibodies. These neutralizing antibodies have been narrow in the focus of their action and specific almost entirely to the strain of the innoculating virus. Additionally, controversy has been reported about both the design of assay systems to measure the neutralization of such isolates and interpretation of the results. Researchers are now looking for a "broad-spectrum" vaccine; however, the high variability of the HIV envelope glycoprotein and its rapid rate of mutation creates an elusive target. Safety concerns have reduced interest in live attenuated virus or whole killed virus vaccines. Some novel approaches being taken include increasing cytotoxic T-lymphocyte responses, induction of immune responses in mucosal tissue surfaces, peptide-based vaccines, oligomeric envelope protein-based vaccine regimens, recombinant Tat protein vaccines, natural killer T-cell (NKT) ligand serving as adjuvant, and fusion of SIV gag with the extracellular domain of CTLA-4 as adjuvant. Most of the HIV vaccines currently in development are the products of recombinant DNA technology.