Safety and efficacy of a cytomegalovirus glycoprotein B (gB) vaccine in adolescent girls: A randomized clinical trial

Bernstein, David I.; Muñoz, Flor M.; Callahan, S. Todd; Rupp, Richard; Wootton, Susan H.; Edwards, Kathryn M.; Turley, Christine B.; Stanberry, Lawrence R.; Patel, Shital M.; McNeal, Monica; Pichon, Sylvie; Amegashie, Cyrille; Bellamy, Abbie R.

doi:10.1016/j.vaccine.2015.11.056

Cited by 188 publications

(182 citation statements)

References 22 publications

(31 reference statements)

Supporting

Mentioning

177

Contrasting

Unclassified

Order By: Relevance

“…Drawing upon standard vaccine strategies, the HCMV field has previously attempted to induce potent antiviral immunity by various approaches including attenuation of live viruses (8)(9)(10), formulation of HCMV glycoprotein subunit vaccines (11)(12)(13), use of viral vectors for epitope expression (14)(15)(16), and delivery of single and bivalent DNA plasmid vaccines (17,18). However, our understanding of anti-HCMV humoral immunity is complicated by the number of distinct glycoprotein complexes that contain neutralizing epitopes, most notably glycoprotein B (gB; fusion protein) and the pentameric complex gH/gL/UL128-131A (PC; necessary for entry into epithelial/endothelial cells) (19).…”

Section: Introductionmentioning

confidence: 99%

“…to reach target endpoints in human clinical trials, the HCMV gB subunit vaccine demonstrated moderate (~50%) efficacy at preventing primary HCMV infection, which is promising for future vaccine-development efforts (12,13). Additional retrospective human studies have reported that neutralizing antibodies targeting HCMV surface glycoproteins are correlated with reduced incidence of congenital virus transmission after primary maternal HCMV infection (20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Preexisting antibodies can protect against congenital cytomegalovirus infection in monkeys

Nelson¹,

Cruz²,

Tran³

et al. 2017

JCI Insight

110

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Preexisting antibodies can protect against congenital cytomegalovirus infection in monkeys

Nelson¹,

Cruz²,

Tran³

et al. 2017

JCI Insight

110

View full text Add to dashboard Cite

“…The most recent study of gB/MF59 was conducted in healthy seronegative adolescent girls [69]. This Phase II study was designed to determine safety and efficacy with an end point based on evidence of HCMV infection.…”

Section: Human Trials Of Subunit Gb Vaccinementioning

confidence: 99%

“…Boosting of gB-specific cell-mediated immunity and antibody responses to gB [69] Bernstein et al (2016) Phase II study (gB/MF59 placebo controlled):…”

Section: Hcmv-seropositive Adult Womenmentioning

confidence: 99%

“…In the seronegative patients receiving a transplant from a seropositive donor, the vaccine reduced the length of viremia and the amount of time undergoing ganciclovir treatment. These results are significant since it is known that transplant-associated immune suppression via reduced cell-mediated immunity leads to HCMV disease, however, vaccine induction of gB-specific antibodies can, therefore, assist and again point to being a useful correlate of protection.The most recent study of gB/MF59 was conducted in healthy seronegative adolescent girls [69]. This Phase II study was designed to determine safety and efficacy with an end point based on evidence of HCMV infection.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Human Cytomegalovirus Vaccination: Progress and Perspectives of Recombinant gB

Manghera

McLean

2016

Future Virol.

View full text Add to dashboard Cite

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 ...

show abstract

Current Status of Cytomegalovirus Vaccines: 2016

Schleiss

2016

Encyclopedia of Life Sciences

View full text Add to dashboard Cite

A vaccine against the debilitating effects of congenital cytomegalovirus (CMV) infection is a major public health priority. Vaccines against CMV may also improve the outcome of solid organ and haematopoietic stem‐cell transplantation. In spite of the long‐recognised morbidity caused by CMV infection, progress towards a licenced vaccine has been slow, owing to uncertainties about the key immunological correlates of protective immunity and the optimal vaccine expression approaches to employ. Driven by the encouraging (albeit suboptimal) benefit conferred by a recombinant CMV glycoprotein B (gB) vaccine against CMV infection and disease in recent clinical trials, there is currently increased interest in designing and evaluating a number of candidate vaccines in both preclinical models and controlled trials. Several new CMV vaccine candidates are currently undergoing evaluation in clinical trials. Major challenges must be met before a vaccine can be licenced. Chief among these challenges are: (1) the need to define the optimal constituents of CMV vaccines; (2) the need to define the metrics of protection that would be required for licensure of a vaccine for congenital CMV infection and (3) the necessity of solving the challenge of designing successful vaccines against reinfection. Key Concepts Congenital infection with CMV is the most common congenital viral infection and is responsible for a wide range of birth defects, including sensorineural hearing loss, mental retardation and developmental delay. Primary infection with CMV during pregnancy confers the greatest risk of foetal transmission, but recurrent infections are also common, and these infections can also lead to transmission of CMV with attendant disabilities. Immunity to CMV is complex, and involves both cellular and humoral immune responses. CMV encodes immune evasion genes that complicate the development of protective immunity, help promote reinfection and create challenges for vaccine design. A vaccine for congenital CMV is a major public health priority, but no licenced vaccines exist. Key targets of the humoral immune response to CMV and the cellular immune response include envelope glycoproteins, particularly gB and the PC proteins, and the pp65 and IE1 proteins, respectively. Several clinical trials of both live, attenuated CMV vaccines and subunit vaccines based on recombinant and/or vectored expression of specific immunogens have been conducted. Modest protection against CMV infection has been demonstrated by a recombinant, adjuvanted gB protein subunit vaccine, although the magnitude and duration of protection were suboptimal. Greater public awareness of congenital CMV is required to help drive efforts to develop and licence a protective vaccine.

show abstract

Safety and efficacy of a cytomegalovirus glycoprotein B (gB) vaccine in adolescent girls: A randomized clinical trial

Cited by 188 publications

References 22 publications

Preexisting antibodies can protect against congenital cytomegalovirus infection in monkeys

Preexisting antibodies can protect against congenital cytomegalovirus infection in monkeys

Human Cytomegalovirus Vaccination: Progress and Perspectives of Recombinant gB

Current Status of Cytomegalovirus Vaccines: 2016

Contact Info

Product

Resources

About