Pharmacodynamic testing of a prototype cytomegalovirus vaccine in a human challenge model. (360G-Wellcome-088233_Z_09_Z)

In this study, we will use our well characterised model of HCMV pathogenesis to evaluate a novel candidate HCMV vaccine. Our model, developed by studying this virus directly in humans, identifies exploitable vulnerabilities in the viral lifecycle. Specifically, natural immunity protects, albeit less than 100%, against infection, disease requires a high viral load and measurement of viral dynamics provides a biomarker of immune control. We hypothesise that inducing or boosting immune responses before viral challenge will significantly decrease viral replication. Natural immune responses to HCMV are heterogeneous and vary with time after virus challenge. We will control this variability by studying patients at defined times after transplantation and by using fresh lymphocytes in standardised immunological assays. We will achieve this within the rigours of a randomised controlled trial where patients receive vaccine or placebo. They will consent to close follow-up and research nur ses will proactively contact them to obtain samples. This study design will definitely produce extensive natural history data to define immune correlates of protection against HCMV and will validate the immune biomarkers we identified in previous studies. It may also identify a vaccine preparation with the ability to produce some immunological control of CMV replication.