Lutzky, Viviana PCorban, MonikaHeslop, LeaMorrison, Leanne E.Crooks, PaulineHall, David FComan, WilliamThomson, ScottMoss, Denis J2015-12-100022-538Xhttp://hdl.handle.net/1885/39078Epstein-Barr virus (EBV) is associated with several malignant diseases including nasopharyngeal carcinoma (NPC), a common neoplasm throughout southeast Asia. Radiotherapy and chemotherapy can achieve remission, but a reemergence of disease is not uncommon. Therefore, there is a need for specific therapies that target the tumor through the recognition of EBV antigens. In NPC, latent membrane protein 1 (LMP1) and LMP2 offer the best opportunity for specific targeting since they are typically expressed and T-cell determinants in each of these proteins have been defined. We have attempted to maximize the opportunity of incorporating every possible CD4 and CD8 determinant in a single formulation. We have achieved this by generating a scrambled protein incorporating random overlapping peptide sets from EBNA1, LMP1, and LMP2, which was then inserted into a replication-deficient strain of adenovirus (adenovirus scrambled antigen vaccine [Ad- SAVINE]). This report describes the construction of this Ad-SAVINE construct, its utility in generating LMP1 and LMP2 responses in healthy individuals as well as NPC patients, and its capacity to define new epitopes. This formulation could have a role in NPC immunotherapy for all ethnic groups since it has the potential to activate all possible CD4 and CD8 responses within EBNA1 and LMPs.Keywords: adenovirus scrambled antigen vaccine; cancer vaccine; CD4 antigen; CD8 antigen; Epstein Barr virus antigen; Epstein Barr virus antigen 1; latent membrane protein 1; latent membrane protein 2; unclassified drug; Adenovirus; article; cancer immunotherapy; C201010.1128/JVI.01303-092016-02-24