Human cytomegalovirus vaccine: time to look for alternative options

In 1999, the Institute of Medicine (IOM) of the National Academy of Sciences (USA) assigned the highest priority for a vaccine to prevent congenital human cytomegalovirus (HCMV) infection, on the basis of the life-time cost to the health care system and the impact of the virus on human suffering. Subsequently, this priority was also endorsed by the US National Vaccine Program Office, which proposed a series of recommendations including support for increased funding by government agencies for HCMV vaccine research. Despite numerous attempts over the past three decades, successful licensure of a HCMV vaccine formulation remains elusive. Here we review the current status of HCMV vaccine studies and, based on our recent understanding of immune regulation of HCMV infection, we argue that a more realistic goal for vaccine strategies should be preventing HCMV disease rather than infection.