Background:  Development of an HIV vaccine is a public health priority. A variety of non-human primate studies have indicated that both neutralizing antibodies and adaptive T cell responses, especially CD8⁺ T cell responses, can prevent experimental challenge and/or control viremia post-experimental infection with primate lentiviruses. The recent failure of monomeric gp120 vaccines has been a vivid demonstration of the need to develop new approaches to elicit neutralizing antibodies to circulating strains of HIV-1. At present, most of the emphasis on HIV vaccines has therefore been directed at approaches to induce HIV-1 CD8⁺ T cells and to evaluate whether such responses can reduce set-point viremia and potentially secondary transmission of the virus to others. In non-human primates, a sustained reduction in set-point viremia has been produced by vaccination with a variety of DNA and viral vector based vaccines. Human clinical trials of both DNA vaccines and poxvirus vectors have had, in most cases, disappointing immunogenicity, albeit 1 phase 3 trial of a canarypox clade B/E vaccine is being conducted in Thailand. To date the most immunogenic cytotoxic leukocyte (CTL)-inducing vaccine approaches have utilized recombinant replication defective adenovirus.

Conclusions:  The 2 leading candidates are a recombinant Ad5 vector containing gag-pol-nef made by Merck Corporation, and a multivalent DNA followed by Ad5 vaccine made by the NIH Vaccine Research Center. These vaccines are entering advanced clinical trials and a review of their immunogenicity and approaches to evaluate their potential efficacy in humans will be discussed.