Potential of Anti-CMV Immunoglobulin Cytotect CP® In Vitro and Ex Vivo in a First-Trimester Placenta Model

Perrine Coste Mazeau; Chloé Jacquet; Clotilde Muller; Mathis Courant; Chahrazed El Hamel; Thierry Chianea; Sébastien Hantz; Sophie Alain

doi:10.3390/microorganisms10040694

Potential of Anti-CMV Immunoglobulin Cytotect CP^® In Vitro and Ex Vivo in a First-Trimester Placenta Model

Microorganisms. 2022 Mar 23;10(4):694. doi: 10.3390/microorganisms10040694.

Authors

Perrine Coste Mazeau^{1

2

3

4}, Chloé Jacquet^{1

2

3}, Clotilde Muller^{1

2}, Mathis Courant², Chahrazed El Hamel⁵, Thierry Chianea⁶, Sébastien Hantz^{1

2

3}, Sophie Alain^{1

2

3}

Affiliations

¹ RESINFIT, UMR1092, University of Limoges, 2 Rue du Pr Descottes, 87000 Limoges, France.
² National Institute of Health and Medical Research INSERM, UMR 1092, 2 Rue du Pr Descottes, 87000 Limoges, France.
³ National Reference Center for Herpesviruses, Virology Department, CHU Limoges, 2 Rue Martin Luther King, 87000 Limoges, France.
⁴ Gynecology and Obstetrics Department, CHU Limoges, 87000 Limoges, France.
⁵ Mother and Child Biobank (CB-HME), Pediatric Department, Hôpital de la Mère et de l'Enfant, CHU Limoges, 87000 Limoges, France.
⁶ Department of Biochemistry and Molecular Genetics, CHU Limoges, 87000 Limoges, France.

Abstract

Background: Congenital CMV infection is the leading cause of neonatal neurological deficit. We herein studied in vitro and ex vivo the potential of the hyperimmune globulin Cytotect CP^® (Biotest, Germany) for congenital infection prevention and treatment.

Methods: In vitro neutralization assays were conducted in fibroblasts and retinal epithelial cells on the CMV strains TB40/E and VHL/E to determine the 50% and 90% neutralizing doses (ND50 and ND90). The toxicity was assessed by measuring LDH release. Ex vivo assays were conducted in first-trimester villi explants with the TB40/E strain, namely, neutralization assays, the prevention of villi infection, and the inhibition of viral replication in infected villi. Viability was assessed by β-HCG quantification in supernatants.

Results: The in vitro neutralization tests showed that Cytotect CP^®® inhibits the development of infection foci (DN50: 0.011-0.014 U/mL for VHL/E and 0.032-0.033 U/mL for TB40E) without any toxicity. In the ex vivo neutralization assays, the DN50 were 0.011 U/mL on day 7 and 0.093 U/mL on day 14. For the prevention of villi infection, the EC50 was 0.024 U/mL on day 7. Cytotect-CP^® did not inhibit viral growth in infected villi. No impact on villi viability was observed.

Conclusions: These results sustained that Cytotect CP^® has the potential to prevent CMV congenital infection.

Keywords: Cytotect CP®; congenital cytomegalovirus; hyperimmune immunoglobulins.