Human Cytomegalovirus Vaccination: Progress and Perspectives of Recombinant gB

Abstract

A vaccine for Human cytomegalovirus (HCMV) remains a high priority as complications following infection are observed in immunocompromised individuals and in congenitally infected neonates. Numerous preclinical and clinical studies have investigated vaccine strategies ranging from live attenuated preparations, nucleic acid-based approaches and recombinant delivery systems to subunit vaccines. These have defined the importance of both cell-mediated and humoral immunity to viral gB in the control of HCMV infection. This review will cover clinical trials investigating vaccine approaches that have incorporated gB and discuss the future perspectives of the recombinant gB subunit vaccine for HCMV. BackgroundHuman cytomegalovirus (HCMV) is a ubiquitous pathogen, known to infect all human populations worldwide [1]. It is an enveloped dsDNA virus that is the largest member of the Herpesviridae family that also includes important pathogens, such as HSV-1 and HSV-2, EBV and varicella zoster virus (VZV), all of which are widespread in human populations [2]. The HCMV genome is approximately 230 kbp encoding 200-250 open reading frames, many of which facilitate immune evasion [3]. A recent study of the HCMV genome and translation products has suggested that it may be even more complex than anticipated with regulation of alternate transcripts allowing for numerous polypeptides to be expressed [4]. Transmission of HCMV predominantly occurs via body fluids, such as saliva, blood, urine and breast milk, leading to contact of the mucosal surfaces, primarily infecting epithelial and endothelial cells, followed by dissemination to numerous organs and tissues [5]. HCMV is, therefore, able to infect a wide range of cells including endothelial cells, epithelial cells, fibroblasts, smooth muscle cells, leukocytes and dendritic cells [5,6]. Similarly to other Herpesviridae family members, HCMV is capable of both lytic and latent infections [7], but primary infection and reactivation from latency are often asymptomatic in immunocompetent individuals [8]. HCMV infection and reactivation in both solid organ and hematopoietic stem cell transplant recipients, and fetal exposure in utero poses a major threat. Immunocompromised individuals, including AIDS patients [9,10] and transplant patients [11,12], are at increased risk of both reactivation or reinfection, and primary HCMV infection has serious consequences for the developing fetus in pregnant women [8]. It is estimated that HCMV congenital infection occurs in 0.5-2% of all annual pregnancies [13], and approximately 10% of infants with congenital HCMV infection present with clinical manifestations at birth, such as hearing loss and neurological developmental defects [14]. Additionally, late-onset hearing disorders can occur with both symptomatic and asymptomatic congenital infection, which [17], which may also be effective in treating congenital infections [18]. Based on the widespread prevalence of HCMV, limited treatment options and the potential for significant morbidity, an effective ...

IgA binds to the AD‐2 epitope of glycoprotein B and neutralizes human cytomegalovirus

“…The AD‐3 epitope was identified within the gB cytoplasmic domain and is a target of non‐neutralizing Abs 16 . Thus, the knowledge of gB epitope‐based Abs has increased in recent years and coupled with the development of recombinant gB as a subunit vaccine 23 demonstrates its importance.…”

Identification of a Continuous Neutralizing Epitope within UL128 of Human Cytomegalovirus

“…Most subunit vaccine strategies have focused on envelope glycoprotein B (gB) as an immunogen based on its essential role in HCMV entry, abundance in the virion envelope, and immunodominance in eliciting fibroblast (FB)-specific NAb in HCMV-seropositive (HCMV ϩ ) individuals (16,17). These efforts culminated in the clinical findings obtained with gB admixed in the adjuvant MF59, showing efficacy rates of 50% and 43% in preventing primary infection in HCMV-seronegative (HCMV Ϫ ) women and adolescent girls, respectively and an ability to significantly reduce viremia in transplant patients (18)(19)(20).…”