This proposal describes an integrated and project-managed collaboration of UK academic groups to study diverse potential HIV vaccine constructs and immunization strategies. The overarching principle is the comparative clinical study of GMP products bearing common HIV inserts, using short schedule, small scale clinical trials in healthy volunteers. The potential vaccine constructs include DNA plasmids, attenuated poxviruses (NYVAC, Fowlpox), rBCG, Adenoviruses(Ad-5 and Ad-11) and a recombinant en velope glycoprotein. All constructs contain the HIV-1 subtype C, codon-optimised CN54 gag-pol-nef-env sequences, and the trimeric rgp140. These diverse constructs with identical inserts will allow, in most cases for the first time, direct comparison of the immunogenicity of diverse vaccine strategies in man. The UKHVC will be organized through a hub and spoke structure. The UKHVC hub (this application) will be responsible for coordination, project management, GMP production, toxicology, r egulatory support, core laboratory support and generic clinical trials support. The UKHVC spokes will be individual project grants submitted to funding agencies, covering scientific development of the constructs, small animal studies, non-reagent costs of the immunological assays required to undertake the trials and specific trial costs, including research staff. Spoke proposals will need to demonstrate evidence of strategic integration with the hub.