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-SIVgag vaccines have elicited cellular responses that control intravenous infection with an HIV/SIV chimeric immunodeficiency virus (SHIV), while replication-competent Ad-SIVenv/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 replicationcompetent 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. :178-185 Correspondence to: Marjorie Robert-Guroff NIH, NCI, 41 Library Drive, Building 41, Room D804, Bethesda, MD 20892-5055, USA Phone: 301-496-2114 Fax: 301-496-8394 E-mail: guroffm@mail.nih.gov Introduction Like HIV, human adenoviruses (Ads) were discovered almost simultaneously by two independent research teams: one searching for the “common cold” virus in cultured human tonsils and adenoids1, and the other searching for the etiologic agent of an “influenza-like” Acute Respiratory Disease (ARD) of army recruits2 in the 1950’s. Since then, at least 51 different human Ad serotypes have been identified as the etiologic agents of respiratory, gastrointestinal, urinary and ocular infections3. These human Ad serotypes can be further grouped into six species (A-F, formerly called subgenera) based on their hemagglutinating properties and biophysical and biochemical criteria4. Ad virions are larger than HIV; their structure is that of a non-enveloped icosahedron, measuring approximately 880 angstroms in diameter5. The inner core contains double-stranded viral DNA, which accounts for up to 13.5% of the virion’s mass. The 12 vertices on the outer shell are made