Cytomegalovirus Vaccines: Current Status and Future Prospects

Abstract

Congenital human cytomegalovirus (HCMV) infection can result in in severe and permanent neurological injury in newborns, and vaccine development is accordingly a major public health priority. HCMV can also cause disease in solid organ (SOT) and hematopoietic stem cell transplant (HSCT) recipients, and a vaccine would be valuable in prevention of viremia and end-organ disease in these populations. Currently there is no licensed HCMV vaccine, but progress toward this goal has been made in recent clinical trials. A recombinant HCMV glycoprotein B (gB) vaccine has been shown to have some efficacy in prevention of infection in young women and adolescents, and provided benefit to HCMV-seronegative SOT recipients. Similarly, DNA vaccines based on gB and the immunodominant T-cell target, pp65 (ppUL83), have been shown to reduce viremia in HSCT patients. This review provides an overview of HCMV vaccine candidates in various stages of development, as well as an update on the current status of ongoing clinical trials. Protective correlates of vaccine-induced immunity may be different for pregnant woman and transplant patients. As more knowledge emerges about correlates of protection, the ultimate licensure of HCMV vaccines may reflect the uniqueness of the target populations being immunized.

The pentameric complex of human Cytomegalovirus: cell tropism, virus dissemination, immune response and vaccine development

“…As a result, several investigators have suggested including the PC in vaccine designs [112]. However, to date, no phase I trial has been completed with a vaccine containing the PC alone.…”

Estimation of the worldwide seroprevalence of cytomegalovirus: A systematic review and meta‐analysis

“…Given the complex natural history of CMV infection, the emerging need to plan the evaluation of candidate vaccines against CMV (which may be given to prevent primary infection and/or to the boost immunity in those with natural infection) would be facilitated by knowledge of the seroepidemiology of CMV around the world. We therefore conducted a systematic literature search to identify the parts of the world that have a relatively high burden of infection with this common virus.…”

New advances in the management of cytomegalovirus in allogeneic haemopoietic stem cell transplantation

“…Immunisation against CMV could potentially reduce or prevent CMV disease. Results from a recent phase III HELIOS trial did not demonstrate improvement in overall survival or a reduction in CMV end‐organ disease in CMV‐seropositive HSCT recipients that received ASP0113, a bivalent DNA vaccine that encodes CMV glycoprotein B and phosphoprotein 65 antigens . CSJ148 is a combination of two monoclonal antibodies (LJP538 and LJP539) directed against CMV glycoproteins that has been recently studied in preventing CMV disease in HSCT recipients .…”