Limited Effector Memory B-Cell Response to Envelope Glycoprotein B During Primary Human Cytomegalovirus Infection

Dauby, Nicolás; Sartori, Delphine; Kummert, Caroline; Lecomte, Sandra; Haelterman, Edwige; Delforge, Marie-Luce; Donner, Cathérine; Mach, Michael; Marchant, Arnaud

doi:10.1093/infdis/jiv769

Cited by 8 publications

(5 citation statements)

References 42 publications

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“…Even though findings from studies of allograft transplant recipients have repeatedly demonstrated an essential role of HCMV-specific T lymphocytes but not antiviral antibodies in control of HCMV infections in immunocompromised populations, the role of antiviral antibody responses, including those responses induced by prophylactic vaccines, has and continues to remain a central theme in studies of protective adaptive immunity in cCMV infections that follow maternal HCMV infections during pregnancy. Decades of studies have described characteristics of maternal anti-HCMV antibody responses including the kinetics of antiviral antibody development, specificities of the antiviral antibody response, and quantities of maternal anti-HCMV antibodies [82][83][84][85][86][87][88][89][90]. Although in some cases results from these studies were correlated with decreased rates of maternal to fetal transmission and the incidence of severe cCMV infections, the variability of responses between individual women in these studies suggests that a direct and perhaps quantitative relationship between anti-HCMV antibody responses and the outcome of maternal infection for an individual woman will be difficult to define.…”

Section: Antiviral Antibodies and The Natural History Of Congenital Hmentioning

confidence: 99%

Role of antibodies in confining cytomegalovirus after reactivation from latency: three decades’ résumé

Krmpotić

Podlech

Reddehase

et al. 2019

Med Microbiol Immunol

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Cytomegaloviruses (CMVs) are highly prevalent herpesviruses, characterized by strict species specificity and the ability to establish non-productive latent infection from which reactivation can occur. Reactivation of latent human CMV (HCMV) represents one of the most important clinical challenges in transplant recipients secondary to the strong immunosuppression. In addition, HCMV is the major viral cause of congenital infection with severe sequelae including brain damage. The accumulated evidence clearly shows that cellular immunity plays a major role in the control of primary CMV infection as well as establishment and maintenance of latency. However, the efficiency of antiviral antibodies in virus control, particularly in prevention of congenital infection and virus reactivation from latency in immunosuppressed hosts, is much less understood. Because of a strict species specificity of HCMV, the role of antibodies in controlling CMV disease has been addressed using murine CMV (MCMV) as a model. Here, we review and discuss the role played by the antiviral antibody response during CMV infections with emphasis on latency and reactivation not only in the MCMV model, but also in relevant clinical settings. We provide evidence to conclude that antiviral antibodies do not prevent the initiating molecular event of virus reactivation from latency but operate by preventing intra-organ spread and inter-organ dissemination of recurrent virus.

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Section: Antiviral Antibodies and The Natural History Of Congenital Hmentioning

confidence: 99%

Role of antibodies in confining cytomegalovirus after reactivation from latency: three decades’ résumé

Krmpotić

Podlech

Reddehase

et al. 2019

Med Microbiol Immunol

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“…Namely, whereas IgG3 responses to tegument proteins showed the typical pattern and decreased while IgG1 responses were stable or increased, IgG3 responses to pentamer increased while IgG1 responses remained largely stable. Memory B cells (MBC) specific for gB are known to exhibit phenotypic states distinct from those specific for tegument antigens 50 . The reduced frequency of MBCs with effector potential specific for glycoprotein as compared to tegument observed in this prior study may relate to the altered kinetics of IgG subclasses observed here.…”

Section: Discussionmentioning

confidence: 99%

Discrimination of Primary and Chronic CMV Infection based on Humoral Immune Profiles in Pregnancy

Hederman,

Remmel,

Sharma

et al. 2024

Preprint

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Most humans have been infected by Cytomegalovirus (CMV) by the time they reach forty years of age. Whereas most of these CMV infections are well controlled by the immune system, congenital infection can lead to serious health effects and death for the fetus and neonate. With clear evidence that risk to the fetus is lower during chronic maternal infection, and varies in association with gestational age at the time of primary maternal infection, further research on humoral immune responses to primary CMV infection during pregnancy is needed. Here, systems serology tools were applied to characterize antibody responses to CMV infection among pregnant and non-pregnant women experiencing either primary or chronic infection. Whereas strikingly different antibody profiles were observed depending on infection status, more limited differences were associated with pregnancy status. Beyond known differences in IgM responses that are used clinically for identification of primary infection, distinctions observed in IgA and FcγR binding antibody responses and among viral antigen specificities accurately predicted infection status in a cross-sectional cohort. Leveraging machine learning, longitudinal samples were also used to define an immunological clock of CMV infection from primary to chronic states and predict time since primary infection with high accuracy. Humoral responses diverged over time in an antigen-specific manner, with IgG3 responses toward tegument decreasing over time as is typical of viral infections, while those directed to pentamer and glycoprotein B were lower during acute and greatest during chronic infection. In sum, this work provides new insights into the antibody response associated with CMV infection status in the context of pregnancy, revealing aspects of humoral immunity that have the potential to improve CMV diagnostics and to support clinical trials of interventions to reduce mother-to-fetus transmission of CMV.

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“…Frequencies of peripheral blood B-cell subsets were analyzed by flow cytometry as previously described. 15 , 32 PBMCs were stained with the following fluorescent monoclonal antibodies: CD3-V500, CD19-PECy7, CD27-BV421, CD20-BV650, CD21-PECF594, CD38-APC, CD138-PE (BD). B-cell subsets were identified using the markers and the gating strategy depicted Supplementary Figure S1 .…”

Section: Methodsmentioning

confidence: 99%

“…Frequencies of antigen-specific IgG-producing memory B-cells (MBC) were measured by ELISPOT assay as previously described. 32 Five million PBMCs were stimulated with CpG ODN2006 (InvivoGen), hCD40Ligand (Cell Signaling Technology), and IL-21 (Miltenyi Biotec) at 37 °C. After 5 days, 200,000 cells were incubated for 1 h at 37 °C in HTS filter plates (MerckMillipore) previously coated with 10 μg/mL PT, FHA, and PRN, and 5 μg/mL TT.…”

Section: Methodsmentioning

confidence: 99%

HIV-related immune activation attenuates polyfunctional IgG and memory B-cell responses to Tdap immunization during pregnancy

Taton,

Willems,

Widomski

et al. 2024

eBioMedicine

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Limited Effector Memory B-Cell Response to Envelope Glycoprotein B During Primary Human Cytomegalovirus Infection

Cited by 8 publications

References 42 publications

Role of antibodies in confining cytomegalovirus after reactivation from latency: three decades’ résumé

Role of antibodies in confining cytomegalovirus after reactivation from latency: three decades’ résumé

Discrimination of Primary and Chronic CMV Infection based on Humoral Immune Profiles in Pregnancy

HIV-related immune activation attenuates polyfunctional IgG and memory B-cell responses to Tdap immunization during pregnancy

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