Antigen Presentation by Epithelial Stem Cells to Promote Life Long Immunity

The nature of the HIV virus has created several barriers to effective immune control by the humoral and cellular arms of adaptive immunity leading to chronic viral replication. Of the vaccine approaches tested in the SIV/macaque model, vaccination with live attenuated lentiviruses has consistently yielded the most effective and durable protection against pathogenic heterologous SIV strains. However, safety issues preclude the use of live attenuated lentiviruses in humans. Our concept is to target epithelial stem cells with a lentivirus vector to introduce an antigen construct under the control of the involucrin promoter. These cells will carry the construct without being attacked by the immune system because they do not express the antigens. As the progeny cells differentiate, the promoter will become activated and the daughter cells will become, in a sense, antigen presenting cells leading to induction of humoral and cellular immune response via direct priming and cross-priming.