Identification of Elite Neutralizers With Broad and Potent Neutralizing Activity Against Human Cytomegalovirus (HCMV) in a Population of HCMV-Seropositive Blood Donors
Identification of Elite Neutralizers With Broad and Potent Neutralizing Activity Against Human Cytomegalovirus (HCMV) in a Population of HCMV-Seropositive Blood Donors
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DOI：
10.1093/infdis/jiy229
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发表时间：
2018-09-15
影响因子：
6.4
通讯作者：
Sinzger, Christian
中科院分区：
文献类型：
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作者：
Falk, Jessica Julia;Winkelmann, Martina;Sinzger, Christian
为了提高抗人巨细胞病毒 (HCMV) 免疫球蛋白制剂的效力，我们打算在 9000 名 HCMV 血清阳性献血者中寻找精英中和剂。我们通过高通量筛选确定了前 2.6% 的中和剂，并进一步分析了具有最有效血浆的应变无关活性的 80 种中和剂。其中，58 种对各种 HCMV 毒株具有广泛的中和活性，因此被视为精英中和剂。然后对所有精英中和剂进行分析，以确定它们在进入过程中对单个病毒颗粒的影响。大多数样本的血浆样本优先抑制病毒渗透，而其中 2 个样本的血浆样本异常出色，可以防止病毒吸附到细胞上。此外，来自 3 种随机选择的精英中和剂的血浆样品的中和能力比商业免疫球蛋白高出 10 倍。在对 6 名选定捐献者的回顾性分析中，重复捐献者的抗 HCMV 中和滴度在 5 年来一直保持在较高水平。总之，来自精英中和供体的血浆样本可以考虑改善基于抗体的 HCMV 感染治疗。
To improve the potency of anti-human cytomegalovirus (HCMV) immunoglobulin preparations, we intended to find elite neutralizers among 9000 HCMV-seropositive blood donors. We identified the top 2.6% neutralizers by use of high-throughput screening and further analyzed the 80 neutralizers with the most effective plasma for strain-independent activity. Of those, 58 had broad neutralizing activity against various HCMV strains and hence were regarded as elite neutralizers. All elite neutralizers were then analyzed to determine their effect on individual virus particles during entry. Most had plasma specimens that preferentially inhibited viral penetration, whereas 2 had exceptional plasma specimens that prevented adsorption of virus to cells. Furthermore, the neutralizing capacity of plasma samples from 3 randomly chosen elite neutralizers was up to 10-fold higher than that for commercial immunoglobulins. In a retrospective analysis of 6 selected donors, anti-HCMV neutralization titers in repeated donations were constantly high over 5 years. In conclusion, plasma samples from elite-neutralizing donors can be considered to improve antibody-based treatment of HCMV infections.