Protection against Congenital CMV Infection Conferred by MVA-Vectored Subunit Vaccines Extends to a Second Pregnancy after Maternal Challenge with a Heterologous, Novel Strain Variant

Maternal reinfection of immune women with novel human cytomegalovirus (HCMV) strains acquired during pregnancy can result in symptomatic congenital CMV (cCMV) infection. Novel animal model strategies are needed to explore vaccine-mediated protections against maternal reinfection. To investigate this in the guinea pig cytomegalovirus (GPCMV) model, a strictly in vivo-passaged workpool of a novel strain, the CIDMTR strain (dose, 1 × 107 pfu) was used to infect dams that had been challenged in a previous pregnancy with the 22122 strain, following either sham-immunization (vector only) or vaccination with MVA-vectored gB, gH/gL, or pentameric complex (PC) vaccines. Maternal DNAemia cleared by day 21 in the glycoprotein-vaccinated dams, but not in the sham-immunized dams. Mean pup birth weights were 72.85 ± 10.2, 80.0 ± 6.9, 81.4 ± 14.1, and 89.38 ± 8.4 g in sham-immunized, gB, gH/gL, and PC groups, respectively (p < 0.01 for control v. PC). Pup mortality in the sham-immunized group was 6/12 (50%), but reduced to 3/35 (8.6%) in combined vaccine groups (p = 0.0048). Vertical CIDMTR transmission occurred in 6/12 pups (50%) in the sham-vaccinated group, compared to 2/34 pups (6%) in the vaccine groups (p = 0.002). We conclude that guinea pigs immunized with vectored vaccines expressing 22122 strain-specific glycoproteins are protected after a reinfection with a novel, heterologous clinical isolate (CIDMTR) in a second pregnancy.

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Intra-uterine transmission of cytomegalovirus in women known to be immune before conception

Journal of Hygiene ◽

10.1017/s0022172400064068 ◽

1984 ◽

Vol 92 (1) ◽

pp. 89-95 ◽

Cited By ~ 9

Author(s):

P. D. Griffiths ◽

C. Baboonian

Keyword(s):

Prospective Study ◽

Pregnant Women ◽

Congenital Infection ◽

Infected Child ◽

Cmv Infection ◽

Previous Pregnancy ◽

Congenital Cmv Infection ◽

Retrospective Testing ◽

A Prospective Study ◽

Congenital Cmv

SUMMARYA prospective study identified 785 pregnant women who had been shown to possess complement fixing antibodies against cytomegalovirus (CMV) during a previous pregnancy. As these women were thus known to have been immune prior to their subsequent conception, their neonates were examined for evidence of congenital CMV infection. Specimens were obtained from 725(92%) of the neonatcs and congenital infection was found in only one (0·14%). The elder sister of the infected child was also shown, by retrospective testing of her stored cord serum for specific IgM antibodies, to have been infected in utero. Thus, one woman was identified who had delivered consecutive siblings congenitally infected with CMV. We conclude that some women have a propensity for intra-uterine transmission of CMV, despite being immune prior to conception, and speculate that such women may have acquired their infections perinatally.

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

Journal of Virology ◽

10.1128/jvi.00283-16 ◽

2016 ◽

Vol 90 (17) ◽

pp. 7902-7919 ◽

Cited By ~ 19

Author(s):

K. Yeon Choi ◽

Matthew Root ◽

Alistair McGregor

Keyword(s):

Guinea Pig ◽

Small Animal ◽

Congenital Infection ◽

T Cell Response ◽

Control Group ◽

Cmv Infection ◽

Vaccine Strategy ◽

Congenital Cmv Infection ◽

Guinea Pig Cytomegalovirus ◽

Congenital Cmv

ABSTRACTCongenital 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 thisdisabledinfectioussingle-cycle (DISC) vaccine strategy, a GPCMV mutant virus was used that lacked the ability to express an essential capsid gene (theUL85homologGP85) 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 (105PFU). 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. Thisdisabledinfectioussingle-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.

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Recombinant Expression of Guinea Pig Cytomegalovirus (GPCMV) Glycoprotein B: Analysis of Antibody Responses Following Vaccination of Guinea Pigs for Prevention of Experimental Congenital CMV Infection • 1474

Pediatric Research ◽

10.1203/00006450-199804001-01495 ◽

1998 ◽

Vol 43 ◽

pp. 252-252

Author(s):

Mark R Schleiss ◽

Nigel Bourne ◽

David I Bernstein

Keyword(s):

Guinea Pig ◽

Guinea Pigs ◽

Recombinant Expression ◽

Antibody Responses ◽

Glycoprotein B ◽

Cmv Infection ◽

Congenital Cmv Infection ◽

Guinea Pig Cytomegalovirus ◽

Congenital Cmv

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In vivo magnetic resonance imaging evidence of olfactory bulbs changes in a newborn with congenital Citomegalovirus: a case report

Italian Journal of Pediatrics ◽

10.1186/s13052-021-01170-w ◽

2021 ◽

Vol 47 (1) ◽

Author(s):

Andrea Bianchi ◽

Caterina Coviello ◽

Valentina Leonardi ◽

Michele Luzzati ◽

Stefano Chiti ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Olfactory System ◽

Resonance Imaging ◽

Cmv Infection ◽

Mri Findings ◽

Olfactory Bulbs ◽

Congenital Cmv Infection ◽

Congenital Cmv

Abstract Background Citomegalovirus (CMV) infects approximately 1% of live newborns. About 10% of the infants affected by congenital CMV infection are symptomatic at birth and up to 60% of these infants will develop permanent neurological disabilities. Depending on gestational age (GA) at the time of infection, the involvement of central nervous system (CNS) can lead to malformations of cortical development, calcifications, periventricular white matter lesions and cysts, ventriculomegaly and cerebellar hypoplasia. Case presentation We report the MRI findings in a Caucasian female born at 32 weeks of post-menstrual age with post-birth diagnosis of congenital CMV infection showing an unusual and peculiar marked T2 hyperintensity of the inner part of olfactory bulbs in addition to the CMV related diffuse brain involvement. Despite the known extensively described fetal and neonatal Magnetic Resonance Imaging (MRI) findings in CMV infected fetuses and newborns, any in vivo MRI depiction of olfactory system damage have never been reported so far. Nevertheless, in murine studies CMV is known to infect the placenta during pregnancy showing particular tropism for neural stem cells of the olfactory system and previous neuropathologic study on CMV infected human fetal brains from 23 to 28 weeks of GA reported damage in the olfactory bulbs (OB) consisting in disseminated cytomegalic cells, inflammation, necrosis and neuronal and radial glial cell loss. Therefore, we assume an OB involvement and damage in congenital CMV infection. Conclusion To our knowledge this is the first in vivo MRI evidence of OB damage in a newborn with congenital CMV infection that may give new insights on CMV infection.

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In Vivo Magnetic Resonance Imaging Evidence of Olfactory Bulbs Changes in a Newborn With Congenital Citomegalovirus: A Case Report

10.21203/rs.3.rs-739238/v1 ◽

2021 ◽

Author(s):

Andrea Bianchi ◽

Caterina Coviello ◽

Valentina Leonardi ◽

Michele Luzzati ◽

Stefano Chiti ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Olfactory System ◽

Resonance Imaging ◽

Cmv Infection ◽

Mri Findings ◽

Olfactory Bulbs ◽

Congenital Cmv Infection ◽

Congenital Cmv

Abstract Background Citomegalovirus (CMV) infects approximately 1% of live newborns. About 10% of the infants affected by congenital CMV infection are symptomatic at birth and up to 60% of these infants will develop permanent neurological disabilities. Depending on gestational age (GA) at the time of infection, the involvement of central nervous system (CNS) can lead to malformations of cortical development, calcifications, periventricular white matter lesions and cysts, ventriculomegaly and cerebellar hypoplasia. Case Presentation: We report the MRI findings in a Caucasian female born at 32 weeks of post-menstrual age with post-birth diagnosis of congenital CMV infection showing an unusual and peculiar marked T2 hyperintensity of the inner part of olfactory bulbs in addition to the CMV related diffuse brain involvement. Despite the known extensively described fetal and neonatal Magnetic Resonance Imaging (MRI) findings in CMV infected fetuses and newborns, any in vivo MRI depiction of olfactory system damage have never been reported so far. Nevertheless, in murine studies CMV is known to infect the placenta during pregnancy showing particular tropism for neural stem cells of the olfactory system and previous neuropathologic study on CMV infected human fetal brains from 23 to 28 weeks of GA reported damage in the olfactory bulbs (OB) consisting in disseminated cytomegalic cells, inflammation, necrosis and neuronal and radial glial cell loss. Therefore, we assume an OB involvement and damage in congenital CMV infection. Conclusion To our knowledge this is the first in vivo MRI evidence of OB damage in a newborn with congenital CMV infection that may give new insights on CMV infection.

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