Preconception Vaccination with a Glycoprotein B (gB) DNA Vaccine Protects against Cytomegalovirus (CMV) Transmission in the Guinea Pig Model of Congenital CMV Infection

Schleiss, Mark R.; Bourne, Nigel; Bernstein, David I.

doi:10.1086/379839

Cited by 46 publications

(32 citation statements)

References 44 publications

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“…This excluded 2 litters reabsorbed by the dams in the control group. In previously published congenital GPCMV infection studies, with a challenge virus dose of 10 5 PFU the mortality rate ranged from 34 to 81% (51,61,(76)(77)(78)(79)(80). The results of the present study fall within this range.…”

Section: Fig 11supporting

confidence: 73%

“…Analysis of viral loads in pup tissues from both groups demonstrated that the tissues from the control nonvaccinated group had a higher frequency of GPCMV-positive tissue (Table 3). A 52.4% reduction in GPCMV transmission in the vaccinated group (23.5% transmission) compared to the control group (75.9% transmission) indicated that the DISC vaccine strategy was more effective than levels reported for studies with live GPCMV vaccine strains (78,80) or gB-based vaccine strategies (76,77,79,82). A comparison of the outcome of our study versus those of previous GPCMV vaccine studies is covered in more detail in the Discussion.…”

Section: Fig 11mentioning

confidence: 66%

“…In contrast, GPCMV gB-specific vaccine strategies produced antibody titers higher than seen for natural convalescent immunity (51,77,79,91), but these gB vaccine strategies were less successful in protecting against congenital infection than was the DISC vaccine. The most effective gB-based vaccine strategies reduced transmission rates from 82 to 45% (gB recombinant baculovirus/GSK adjuvant), 77 to 41% (gB DNA vaccine), and 79 to 59% (MVA gB) (76,77,79). Potentially, a failing of these gB vaccine strategies was that the gB lacked a C-terminal domain and therefore there was an inability of the recombinant gB to multimerize, as seen in natural infection.…”

Section: Discussionmentioning

confidence: 99%

“…The transmission rate in the control group was roughly similar to the congenital GPCMV transmission rate observed for control nonvaccinated groups in other published studies that used challenge virus at a dose of 10 5 PFU. In previous studies, the GPCMV transmission rate ranged from 50 to 85%, with the majority in the range of 65 to 85% (average rate, 74.4%) (51,(76)(77)(78)(79)(80). In one study with a virus challenge dose of 10 6 PFU, the transmission rate was 70% (81), which indicated that a higher dose of challenge virus does not necessarily result in a higher transmission rate.…”

Section: Fig 11mentioning

confidence: 90%

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A Novel Non-Replication-Competent Cytomegalovirus Capsid Mutant Vaccine Strategy Is Effective in Reducing Congenital Infection

Choi

Root

McGregor

2016

J Virol

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Congenital cytomegalovirus (CMV) infection is a leading cause of mental retardation and deafness in newborns. The guinea pig is the only small animal model for congenital CMV infection. A novel CMV vaccine was investigated as an intervention strategy against congenital guinea pig cytomegalovirus (GPCMV) infection. In this disabled infectious single-cycle (DISC) vaccine strategy, a GPCMV mutant virus was used that lacked the ability to express an essential capsid gene (the UL85 homolog GP85) except when grown on a complementing cell line. In vaccinated animals, the GP85 mutant virus (GP85 DISC) induced an antibody response to important glycoprotein complexes considered neutralizing target antigens (gB, gH/gL/gO, and gM/gN). The vaccine also generated a T cell response to the pp65 homolog (GP83), determined via a newly established guinea pig gamma interferon enzyme-linked immunosorbent spot assay. In a congenital infection protection study, GP85 DISC-vaccinated animals and a nonvaccinated control group were challenged during pregnancy with wild-type GPCMV (10 5 PFU). The pregnant animals carried the pups to term, and viral loads in target organs of pups were analyzed. Based on live pup births in the vaccinated and control groups (94.1% versus 63.6%), the vaccine was successful in reducing mortality (P ‫؍‬ 0.0002). Additionally, pups from the vaccinated group had reduced CMV transmission, with 23.5% infected target organs versus 75.9% in the control group. Overall, these preliminary studies indicate that a DISC CMV vaccine strategy has the ability to induce an immune response similar to that of natural virus infection but has the increased safety of a non-replication-competent virus, which makes this approach attractive as a CMV vaccine strategy. IMPORTANCECongenital CMV infection is a leading cause of mental retardation and deafness in newborns. An effective vaccine against CMV remains an elusive goal despite over 50 years of CMV research. The guinea pig, with a placenta structure similar to that in humans, is the only small animal model for congenital CMV infection and recapitulates disease symptoms (e.g., deafness) in newborn pups. In this report, a novel vaccine strategy against congenital guinea pig cytomegalovirus (GPCMV) infection was developed, characterized, and tested for efficacy. This disabled infectious single-cycle (DISC) vaccine strategy induced a neutralizing antibody or a T cell response to important target antigens. In a congenital infection protection study, animals were protected against CMV in comparison to the nonvaccinated group (52% reduction of transmission). This novel vaccine was more effective than previously tested gB-based vaccines and most other strategies involving live virus vaccines. Overall, the DISC vaccine is a safe and promising approach against congenital CMV infection. H uman cytomegalovirus (HCMV), a betaherpesvirus, has evolved very closely with its human host. Virus infection in a healthy host is normally asymptomatic but leads to a lifelong infection. In contrast,...

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Section: Fig 11supporting

confidence: 73%

Section: Fig 11mentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Section: Fig 11mentioning

confidence: 90%

See 2 more Smart Citations

A Novel Non-Replication-Competent Cytomegalovirus Capsid Mutant Vaccine Strategy Is Effective in Reducing Congenital Infection

Choi

Root

McGregor

2016

J Virol

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“…Although a larger numbers of Mmu are needed to conWrm this observation, it further indicates the protective role of neutralizing antibodies against CMV [14,17,18,24] and a gB-based vaccine strategy [15,17,25]. Natural immunity studies have suggested that a vaccine that stimulates immunity equivalent to levels associated with natural infection could reduce the morbidity due to congenital CMV infection by »80% [8,9].…”

Section: #6 Controlmentioning

confidence: 93%

Evaluation of recombinant modified vaccinia Ankara virus-based rhesus cytomegalovirus vaccines in rhesus macaques

Yue

Wang

Abel

et al. 2008

Med Microbiol Immunol

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A vaccine consisting of rhesus cytomegalovirus (RhCMV) pp65-2, gB and IE1 expressed via modiWed vaccinia Ankara (MVA) was evaluated in rhesus macaques with or without prior priming with expression plasmids for the same antigens. Following two MVA treatments, comparable levels of anti-gB, pp65-2 and neutralizing antibody responses, and pp65-2-and IE1-speciWc cellular immune responses were detected in both vaccinated groups. Similar reductions in plasma peak viral loads were observed in these groups compared to untreated controls. This study demonstrates the immunogenicity and protective eYcacy of rMVA-based RhCMV subunit vaccines in a primate host and warrants further investigation to improve the eYcacy of subunit vaccines against CMV.

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What We Have Learned from Animal Models of HCMV

Dogra

Sparer

2014

Methods in Molecular Biology

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Although human cytomegalovirus (HCMV) primary infection is generally asymptomatic, in immune-compromised patients HCMV increases morbidity and mortality. As a member of the betaherpesvirus family, in vivo studies of HCMV are limited due to its species specificity. CMVs from other species are often used as surrogates to express HCMV genes/proteins or used as models for inferring HCMV protein function in humans. Using innovative experiments, these animal models have answered important questions about CMV's life cycle, dissemination, pathogenesis, immune evasion, and host immune response. This chapter provides CMV biologists with an overview of the insights gained using these animal models. Subsequent chapters will provide details of the specifics of the experimental methods developed for each of the animal models discussed here.

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Preconception Vaccination with a Glycoprotein B (gB) DNA Vaccine Protects against Cytomegalovirus (CMV) Transmission in the Guinea Pig Model of Congenital CMV Infection

Cited by 46 publications

References 44 publications

A Novel Non-Replication-Competent Cytomegalovirus Capsid Mutant Vaccine Strategy Is Effective in Reducing Congenital Infection

A Novel Non-Replication-Competent Cytomegalovirus Capsid Mutant Vaccine Strategy Is Effective in Reducing Congenital Infection

Evaluation of recombinant modified vaccinia Ankara virus-based rhesus cytomegalovirus vaccines in rhesus macaques

What We Have Learned from Animal Models of HCMV

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