Human vaginal xenografts: a model system for microbicide testing

Abstract

Human, vaginal epithelial xenografts have been established in immunocompromised mice by transplantation of split thickness epithelial tissues to the subcutaneous or renal capsule space. Xenografts in the subcutaneous space are constructed with a patent lumen. Xenografts recapitulate the tissue architecture and biochemical repertoire of intact human vaginal epithelium. Productive infection of xenografts with both herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) has been accomplished. The amphoteric surfactant, C31G, can inactivate HSV-2 in vitro and prevent subsequent xenograft infection. The alkyl sulfate, sodium dodecyl sulfate (SDS) can inactivate HSV-2 and HPV in vitro and prevent subsequent xenograft infection. Pre-application of microbicides to the vaginal lumen was carried out in order to determine tissue response to varying microbicide doses and ability of C31G and SDS to protect from subsequent virus inoculation. These data demonstrate the validity of the human vaginal xenograft model. Xenografts are suitable targets for fastidious human viruses and effectively allow for assessment of both toxicity and efficacy of candidate vaginal microbicides.