Adenoviruses as vectors for HIV vaccines

The tropism of adenoviruses (Ad) for mucosal epithelium makes them ideal vectors for the development of recombinant Ad-HIV vaccines. Currently, several Ad-HIV vaccine candidates are being tested in clinical and preclinical trials. Here, we review the progress on the safety, immunogenicity and efficacy of replication-competent and replication-defective Ad-HIV and Ad-SIV vaccines in animal models, including non-human primates. Replication-defective Ad-SIV gag vaccines have elicited cellular responses that control intravenous infection with an HIV/SIV chimeric immunodeficiency virus (SHIV), while replication-competent Ad-SIV env/rev/gag/nef vaccines have stimulated cellular and humoral responses and protected rhesus monkeys from a mucosal challenge with pathogenic SIV. The composition and advantages of these and other Ad vaccines are described, with particular emphasis on strategies to increase the immunogenicity of the replication-defective vaccines and the safety and efficacy of the replication-competent approach. The overall efficacy of Ad-based vaccines in non-human primates should encourage further evaluation of additional replication-competent and replication-defective Ad-HIV candidates in human trials.