Comparison of cytomegalovirus (CMV)-specific neutralization capacity of hyperimmunoglobulin (HIG) versus standard intravenous immunoglobulin (IVIG) preparations: Impact of CMV IgG normalization

Schampera, Matthias Stefan; Schweinzer, Katrin; Abele, Harald; Kagan, Karl Oliver; Klein, Reinhild; Rettig, Ingo; Jahn, Gerhard; Hamprecht, Klaus

doi:10.1016/j.jcv.2017.03.005

Cited by 22 publications

(23 citation statements)

References 18 publications

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“…The treatment protocol was developed based on an index case and additional in-vitro studies of characteristics of HIG and other standard intravenous immunoglobulin preparations on CMV-specific neutralization capacity 10,12,16 . In the most recent of these studies comparing HIG with standard Ig preparations, we found high CMV-specific IgG antibody-binding capacity as well as very potent antiviral neutralization capacity against human epithelial target cells in both 16 . In the index case, we observed an initial half-life of about 11 days after administration of 200 IU/kg body weight, indicating that a monthly protocol for the administration of HIG is not sufficient.…”

Section: Discussionmentioning

confidence: 99%

Prevention of maternal–fetal transmission of cytomegalovirus after primary maternal infection in the first trimester by biweekly hyperimmunoglobulin administration

Kagan

Enders²,

Schampera

et al. 2019

Ultrasound in Obstet & Gyne

112

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Section: Discussionmentioning

confidence: 99%

Prevention of maternal–fetal transmission of cytomegalovirus after primary maternal infection in the first trimester by biweekly hyperimmunoglobulin administration

Kagan

Enders²,

Schampera

et al. 2019

Ultrasound in Obstet & Gyne

112

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“…Neutralization (NT) assays using human retinal pigment epithelial cells (ARPE-19) were performed as described earlier by Maschmann et al [28] and Schampera et al [29]. As controls, HCMV-seronegative pools of plasma and whey from mothers of the BlooMil study were used.…”

Section: Neutralization Assaysmentioning

confidence: 99%

“…As controls, HCMV-seronegative pools of plasma and whey from mothers of the BlooMil study were used. NT calibration in plasma or whey was done by dilutions of a HIG stock solution (Cytotect®) to concentrations of in vivo HCMV-IgG levels of the seropositive cohort: The mean ECLIA values of the seropositive plasma (720 U/mL) and whey samples (6.4 U/mL) were calibrated by predilution of Cytotect®(4725 U/mL) [29] in medium to both corresponding concentrations (1:6.5 and 1:700 respectively). Then, every control Nutrients 2020, 12, 338 4 of 13 was measured in the same dilution steps as the HCMV-seropositive pools.…”

Section: Neutralization Assaysmentioning

confidence: 99%

“…Only one mother (one of 18, 5.6%) did not reactivate at any of the four time ranges, two mothers (two of 18, 11.1%) showed only a slight increase of viral load at T4. Cytotect® (4725 U/ml) [29] in medium to both corresponding concentrations (1:6.5 and 1:700 respectively). Then, every control was measured in the same dilution steps as the HCMV-seropositive pools.…”

Section: Hcmv-reactivation In Breast Milkmentioning

confidence: 99%

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Human Cytomegalovirus Reactivation During Lactation: Impact of Antibody Kinetics and Neutralization in Blood and Breast Milk

Lazar¹,

Rabe²,

Goelz

et al. 2020

Nutrients

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Human cytomegalovirus (HCMV) is shed into breast milk in nearly every seropositive woman during lactation. This reactivation shows mostly a self-limited, unimodal course. The dynamics and functional role of HCMV-specific-IgG in breast milk and in plasma during reactivation are unknown. Milk whey viral loads were monitored with real-time PCR in 18 HCMV-seropositive mothers over two months postpartum. HCMV-antibody binding assays (ECLIA) and antigen-specific immunoblotting were performed from plasma and corresponding milk samples. Epithelial-cell-specific neutralization was used to analyze functional antibodies in plasma- and whey-pools. Viral loads in milk whey showed unimodal courses in 15 of 18 mothers with peak viral loads around one month postpartum. HCMV-specific-IgG-antibodies increased significantly in plasma and milk whey during reactivation. The mean levels of plasma IgG were about 275-fold higher than in whey. Only antibodies against tegument protein p150 were continuously expressed in both compartments. Anti-glycoprotein-B1 IgG-antibodies were variably expressed in whey, but continuously in plasma. Neutralization assays showed 40-fold higher NT-50 values in plasma compared to whey at two months postpartum. During reactivation, HCMV-specific-IgG reactivities and neutralizing capacities are much lower in whey than in plasma. Therefore, their specific role in the decrease and discontinuation of virus-shedding in milk remains unclear.

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“…Of the remaining candidates, no simple cell culture system is available for EBV, and different neutralization assay formats exist for CMV, with unclear correlation of results with clinical relevance. 25,27,28 HAdV, RSV, and hPIV were thus finally selected for further investigation.…”

Section: Choice Of Alternative Virus Antibody Specificitiesmentioning

confidence: 99%

Immunoglobulins and virus antibody titers: of past needs, current requirements, and future options

Kreil

Farcet

2018

Transfusion

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BACKGROUND Immunoglobulins (Igs) have been in clinical use for almost 70 years, and early on were also used in conjunction with exposure to the measles virus or polio virus. The US regulations that describe functional Ig lot release thus require the demonstration of minimum antibody titers against these two viruses, although the use of vaccines has now dramatically reduced their incidence. The lower clinical importance of these viruses raises the question of whether other virus antibodies might be more informative for patients with immunodeficiency. STUDY DESIGN AND METHODS A literature survey was conducted to identify viruses of potential clinical concern for people with immunodeficiency. The viruses selected have stable seroepidemiology and associated functional antibody assays. As a result, neutralizing antibody titers to human adenovirus 5 (HAdV5), respiratory syncytial virus (RSV) serotypes A and B, and human parainfluenza virus 3 (hPIV3) were determined in Ig lots produced from plasma collected in either the United States or the European Union. RESULTS The virus antibody titers measured were high and consistent among the Ig lots tested. Use of either US‐ or EU‐derived plasma as starting material resulted in equivalent virus antibody titers, with the exception of RSV serotype B, for which a lower titer was seen in EU plasma–derived Ig lots. CONCLUSION With the significant decline in measles virus and polio virus circulation, and even their potential eradication, measurement of antibody titers against other viruses in Ig products may be more informative for functional lot release testing.

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Comparison of cytomegalovirus (CMV)-specific neutralization capacity of hyperimmunoglobulin (HIG) versus standard intravenous immunoglobulin (IVIG) preparations: Impact of CMV IgG normalization

Cited by 22 publications

References 18 publications

Prevention of maternal–fetal transmission of cytomegalovirus after primary maternal infection in the first trimester by biweekly hyperimmunoglobulin administration

Prevention of maternal–fetal transmission of cytomegalovirus after primary maternal infection in the first trimester by biweekly hyperimmunoglobulin administration

Human Cytomegalovirus Reactivation During Lactation: Impact of Antibody Kinetics and Neutralization in Blood and Breast Milk

Immunoglobulins and virus antibody titers: of past needs, current requirements, and future options

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