Abstract
CD8+ T cell responses are an important component of a protective immune response in many pathogenic infections including HIV and Herpesviridae like CMV and EBV. Identifying the pathogen-encoded protective antigens, antigenic heterogeneity, and progressive immune dysfunction are major barriers facing the development of effective CD8+ T cell targeted vaccines. Here we tested the hypothesis that pathogen infected cells can be sensitized to vaccination against host derived antigens presented by the infected cells with reduced TAP expression. We show that natural or targeted downregulation of TAP in CMV and EBV or HIV infected cells, respectively, leads to the presentation of a cell-encoded non-mutated cryptic epitope initially described in tumor cells with reduced TAP expression, and that PBMC derived CD8+ T cells enriched for multiple TAP downregulation-induced epitopes recognized TAPlow CMV, EBV, and HIV infected cells leading the depletion of the TAPlow infected cells and expression of activation markers in the T cells. This study describes a prototype of a universal drug formulation to vaccinate against tumors and pathogen infected cells, dispensing with the need to identify pathogen or tumor specific antigenic targets, and obviating the limitations associated with antigenic heterogeneity and immune dysfunction characteristic of pathogens like HIV.