Update on the current status of cytomegalovirus vaccines

Abstract

Human cytomegalovirus (HCMV) is ubiquitous in all populations, and is the most commonly recognized cause of congenital viral infection in developed countries. On the basis of the economic costs saved and the improvement in quality of life that could potentially be conferred by a successful vaccine for prevention of congenital HCMV infection, the Institute of Medicine has identified HCMV vaccine development as a major public health priority. An effective vaccine could potentially also be beneficial in preventing or ameliorating HCMV disease in immunocompromised individuals. Although there are no licensed HCMV vaccines currently available, enormous progress has been made in the last decade, as evidenced by the recently reported results of a Phase II trial of a glycoprotein B vaccine for the prevention of HCMV infection in seronegative women of childbearing age. HCMV vaccines currently in clinical trials include: glycoprotein B subunit vaccines; alphavirus replicon particle vaccines; DNA vaccines; and live-attenuated vaccines. A variety of vaccine strategies are also being examined in preclinical systems and animal models of infection. These include: recombinant vesicular stomatitis virus vaccines; recombinant modified vaccinia virus Ankara; replication-deficient adenovirus-vectored vaccines; and recombinant live-attenuated virus vaccines generated by mutagenesis of cloned rodent CMV genomes maintained as bacterial artificial chromosomes in Escherichia coli. In this article, we provide an overview of the current state of clinical trials and preclinical development of vaccines against HCMV, with an emphasis on studies that have been conducted in the past 5 years. We also summarize a number of recent advances in the study of the biology of HCMV, particularly with respect to epithelial and endothelial cell entry of the virus, which have implications for future vaccine design.

Development of a High-Throughput Assay To Measure the Neutralization Capability of Anti-Cytomegalovirus Antibodies

“…One study found neutralizing antibodies to gB in 86% of 600 CMV-positive individuals (45). As several CMV vaccine strategies utilize the gB protein as an immunogen, our assay could be ideal for assessing vaccine efficacy (46). We show here (Fig.…”

Cytomegalovirus Vaccine Strain Towne-Derived Dense Bodies Induce Broad Cellular Immune Responses and Neutralizing Antibodies That Prevent Infection of Fibroblasts and Epithelial Cells

“…In contrast to the broader roles for gB, gH/gL/gO, and gM/gN, the gH/gL/UL128/UL130/ UL131A complex is more specialized but is considered to be required for viral entry into specific cell types, including epithelial and endothelial cells (21)(22)(23). A protective vaccine is expected to require neutralizing antibodies that prevent infection of epithelial and endothelial cells (24). In some animal models, the titers of neutralizing antibodies that prevented infection of epithelial and endothelial cells were increased by addition of the gH/gL/UL128/ UL130/UL131A complex to a live virus vaccine (17).…”

Dendritic Cell Targets for Self-Replicating RNA Vaccines

“…Such approaches were also applied in fields other than cancer vaccination [8,59], for example against HIV [58] and influenza [27]. Importantly, self-amplifying replicon RNA vaccines have been trialled as VRPs [56,[66][67][68][69], which demonstrates the high potential for these RNA vaccines when delivered by nanoparticulate vehicles to DCs.…”