Cytomegalovirus vaccines under clinical development

Abstract

Congenital cytomegalovirus (CMV) infection is the most common infectious cause of disability in newborn infants. CMV also causes serious disease in solid organ (SOT) and haematopoietic stem cell transplant (HSCT) recipients. In otherwise healthy children and adults, primary CMV infection rarely causes illness. However, even asymptomatic CMV infections may predispose an individual towards an increased risk of atherosclerosis, cancer and immune senescence over the life course, although such associations remain controversial. Thus, although a vaccine against congenital CMV infection would have the greatest public health impact and cost-effectiveness, arguably all populations could benefit from an effective immunisation against this virus. Currently there are no licensed CMV vaccines, but there is increased interest in developing and testing potential candidates, driven by the demonstration that a recombinant CMV glycoprotein B (gB) vaccine has some efficacy in prevention of infection in young women and adolescents, and in CMV-seronegative SOT recipients. In this review, the recent and current status of candidate CMV vaccines is discussed. Evolving concepts about proposed correlates of protective immunity in different target populations for CMV vaccination, and how these differences impact current clinical trials, are also reviewed.

Keywords: CMV; congenital infection; cytomegalovirus; pentameric complex; placenta; vaccine.

Figure 1.

Schematic representation of the potential targets of a vaccine against congenital CMV infection. Clarity is required regarding the issue of whether a vaccine primarily needs to target the maternal, placental, or fetal compartment. Congenital infection, including attendant sequelae, occurs even in the face of high-titre neutralising antibody in the neonate. The paradox of re-infection with subsequent transmission also needs to be resolved. If sterilising immunity can be achieved in the mother, placental and fetal transmission become moot points. Engendering protective immunity in a vaccine is likely to require robust maternal antibody and T-cell responses, particularly CD4+ responses