New therapeutic perspective in the prevention of congenital cytomegalovirus infection.

Introduction: Hyperimmune globulin Cytotect CP® is a candidate for cytomegalovirus congenital infection prevention. We previously demonstrated its efficacy to prevent villi infection in our first-trimester placenta explants up to day 7, but with an inefficiency at day 14 (Coste-Mazeau et al., Microorganisms, 2021). As this could impact clinical efficacy, we now study the effect of weekly administration of Cytotect CP® on the prevention of villi infection.

Methods: Human embryonic lung fibroblast cells were infected at confluence with the endothelial strain TB40/E. Placentae were collected from voluntary pregnancy terminations (8-14 weeks of gestation) from cytomegalovirus-seronegative women. After 5 days of infection of the cells, villi explants were simultaneously added on sponges with Cytotect CP® at various concentrations. After 7 days, Cytotect CP® was renewed in only half of the plates. Villi were collected at days 7 and 14 with or without medium renewal. We compared the viral load by duplex quantitative PCR cytomegalovirus/albumin and the toxicity by measuring β-hCG concentrations in the supernatants with and without medium renewal.

Results: We did not find any efficacy of Cytotect CP® at day 14 when Cytotect CP® is not renewed, but a regular decrease of the viral load when the immunoglobulins were renewed at day 7, with an EC50 = 0.52 U/mL. We did not observed toxicity of Cytotect CP® with or without renewal of the molecule.

Conclusion: Cytotect CP® is more effective when renewed at day 7. The prevention of congenital cytomegalovirus infection could be enhanced by reducing the spacing of doses.