Auditorium

Cytomegalovirus is a herpesvirus that infects most of the world's population. It usually causes no overt symptoms yet is medically important. In the fetus and in the immunocompromised, uncontrolled replication to high viral loads causes extensive damage to multiple organs revealed by histopathology (direct effects). In the immunocompromised it is associated with a statistical excess of conditions that also occur in the absence of CMV, such as graft rejection, atherosclerosis and death (indirect effects). One of these conditions (death after stem cell transplant) has been significantly reduced in a placebo-controlled trial of a CMV-specific drug, showing that this association is causal. It would be desirable to control the direct and indirect effects through universal immunisation, but CMV represents a formidable vaccine target. As a herpesvirus, it establishes latency, persists for the life of the individual and reactivates. People with prior CMV can also be reinfected with a new strain. The virus encodes multiple immune evasion genes. One approach is to induce immune responses similar to those found after primary infection and determine if these protect against future exposure to CMV. Another approach is to induce selected responses prior to transplant and determine if these, compared to placebo, can reduce the parameters of viral load seen post-transplant. I will describe both of these approaches, the key conclusions so far and review prospects for future control of CMV.