Harnessing cell-mediated immunity to cytomegalovirus for personalised antiviral therapy

Human cytomegalovirus (CMV) establishes lifelong latent infections in most of us. Although CMV does not usually cause severe disease in healthy people, the virus is a leading cause of birth defects and a major pathogen in individuals with weakened immune systems including transplant patients. There is no vaccine for CMV, and antiviral treatment is costly and comes with serious side effects. To inform decision-making for antiviral therapy after transplantation, novel immune-based diagnostic assays are being developed. The immediate-early 1 (IE1) and pp65 proteins, two highly immunogenic CMV antigens, are integral components of many candidate vaccines and diagnostic assays including T-Track® CMV developed by Lophius Biosciences. The student will examine how the two viral proteins contribute to CMV replication and reactivation from latency in human cells. He/she will also optimize IE1 and pp65 protein production in bacterial and mammalian cells and engineer mutant proteins with improved activities in the T-Track® CMV assay. The work will be conducted in a CMV research group (Nevels lab) and at Lophius Biosciences, who have been long-standing collaborators. The results from this study will help improve and personalize the management of CMV infection in immune-suppressed patients, inform vaccine development, and illuminate molecular mechanisms underlying CMV disease.