Protein-based HIV-1 microbicides.

Although the development of a protective vaccine remains the most effective strategy for the global control of HIV/AIDS, another practical form of medical intervention would be a microbicide capable of preventing HIV-1 transmission at the mucosal level. A broad spectrum of antiviral molecules have demonstrated in vitro efficacy in proofof- principle studies, and a selected few have already been tested in pre-clinical and clinical microbicide trials. Nevertheless, major hurdles remain to be overcome and there is still much uncertainty about the choice of inhibitors, formulations and administration vehicles for obtaining a safe and effective microbicide. A special category of HIV-1 microbicides are those based on proteins or peptides that interfere with the earliest steps in the viral infectious cycle. Besides a high degree of target specificity and a limited, if any, systemic absorption, proteinbased microbicides offer the unique advantage of being suitable to in vivo expression by engineered bacteria or viral vectors, which might ensure prolonged protection without the need for planned, intercourse-coordinated application. In this respect, vaginal or rectal microbiota such as Lactobacillus spp. represent ideal expression systems as they would not only produce the inhibitor of choice at the mucosal surface, but also easily blend within the resident microflora and offer additional valuable homeostatic effects. In this article, we review the current state of the art on protein-based microbicides.