Comparison of cytomegalovirus (CMV)-specific neutralization capacity of hyperimmunoglobulin (HIG) versus standard intravenous immunoglobulin (IVIG) preparations: Impact of CMV IgG normalization.
Based on a non-randomized study of Nigro et al. (2005) the intravenous administration of hyperimmunoglobulins (HIGs) is applied frequently to women with primary CMV-infection as "off-label use" in Germany.



In order to describe their CMV-specific neutralization-capacity in vitro, we analyzed the HIG preparations Cytotect®, and Cytogam®as well as the standard intravenous immunoglobulins (IVIG) Octagam®, Gamunex®, Kiovig®.



We performed short-term cell-free CMV neutralization assays (CFNT) and long-term cell-adapted neutralization-plaque-reduction assays (PRANT). Human retinal epithelial cells (ARPE-19) were used as target cells. A clinical CMV primary-isolate from amnion fluid propagated in epithelial cells without any initial fibroblast adaption was used. For calibration we previously generated serum-pools (N=100) from two cohorts of mothers at birth: seronegative and latently CMV-infected mothers. Biochemical analysis included total protein, albumin, Ig-class, and IgG-subclasses. Additionally, CMV antibody-reactivity was checked using recombinant immunoblotting.



HIG and IVIG preparations showed differences in levels and patterns of protein, Ig-class and CMV-specific antibody concentrations. All IgG-preparations showed high in vitro NT-capacity and high IgG-avidity. The NT90-values for HIGs and IVIGs and our seropositive reference-pool showed similar NT-capacity at a dilution of (1:100) which corresponded well to 4.1 PEI-Units/ml.



All HIG- and IVIG-preparations showed similar NT-capacity following CMV IgG-normalization. Our in vitro results are in strong contrast to former findings suggesting higher functional CMV NT titers in IVIG-preparations compared to HIGs.
Institute of Medical Virology, University Hospital of Tuebingen, D-72076 Tuebingen, Germany.
Matthias Stefan
MS
Schampera
Institute of Medical Virology, University Hospital of Tuebingen, D-72076 Tuebingen, Germany.
Katrin
K
Schweinzer
Department of Obstetrics and Gynaecology, University Hospital of Tuebingen, Germany.
Harald
H
Abele
Department of Obstetrics and Gynaecology, University Hospital of Tuebingen, Germany.
Karl Oliver
KO
Kagan
Department of Internal Medicine II, Immunopathological Laboratory; University Hospital of Tuebingen, Germany.
Reinhild
R
Klein
Department of Internal Medicine, Central Laboratory, University Hospital of Tuebingen, Germany.
Ingo
I
Rettig
Institute of Medical Virology, University Hospital of Tuebingen, D-72076 Tuebingen, Germany.
Gerhard
G
Jahn
Institute of Medical Virology, University Hospital of Tuebingen, D-72076 Tuebingen, Germany. Electronic address: klaus.hamprecht@med.uni-tuebingen.de.
Klaus
K
Hamprecht
D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D000998:Antiviral Agents / Q000494:pharmacology*; D003587:Cytomegalovirus / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D009500:Neutralization Tests
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000998:Antiviral Agents; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous
CMV primary infection; Hyperimmunogloblulin (HIG); Neutralizing antibodies; Pregnancy; Recombinant immunoblot; Standard immunoglobulin