抗巨细胞病毒免疫球蛋白Cytotect CP在孕早期胎盘模型中的体外和离体潜力
Potential of Anti-CMV Immunoglobulin Cytotect CP In Vitro and Ex Vivo in a First-Trimester Placenta Model.
作者信息
Coste Mazeau Perrine, Jacquet Chloé, Muller Clotilde, Courant Mathis, El Hamel Chahrazed, Chianea Thierry, Hantz Sébastien, Alain Sophie
机构信息
RESINFIT, UMR1092, University of Limoges, 2 Rue du Pr Descottes, 87000 Limoges, France.
National Institute of Health and Medical Research INSERM, UMR 1092, 2 Rue du Pr Descottes, 87000 Limoges, France.
出版信息
Microorganisms. 2022 Mar 23;10(4):694. doi: 10.3390/microorganisms10040694.
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.
背景
先天性巨细胞病毒（CMV）感染是新生儿神经功能缺损的主要原因。我们在此对超免疫球蛋白Cytotect CP（德国Biotest公司）预防和治疗先天性感染的潜力进行了体外和离体研究。
方法
在成纤维细胞和视网膜上皮细胞中对CMV毒株TB40/E和VHL/E进行体外中和试验，以确定50%和90%中和剂量（ND50和ND90）。通过测量乳酸脱氢酶（LDH）释放评估毒性。在孕早期绒毛外植体中使用TB40/E毒株进行离体试验，即中和试验、绒毛感染预防试验以及感染绒毛中病毒复制的抑制试验。通过检测上清液中的β-人绒毛膜促性腺激素（β-HCG）定量评估活力。
结果
体外中和试验表明，Cytotect CP可抑制感染灶的形成（VHL/E的DN50：0.011 - 0.014 U/mL，TB40E的DN50：0.032 - 0.033 U/mL），且无任何毒性。在离体中和试验中，第7天的DN50为0.011 U/mL，第14天为0.093 U/mL。对于绒毛感染的预防，第7天的EC50为0.024 U/mL。Cytotect-CP未抑制感染绒毛中的病毒生长。未观察到对绒毛活力的影响。
结论
这些结果支持Cytotect CP有预防CMV先天性感染的潜力。
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