Isolation of Human Monoclonal Antibodies That Potently Neutralize Human Cytomegalovirus Infection by Targeting Different Epitopes on the gH/gL/UL128-131A Complex
Isolation of Human Monoclonal Antibodies That Potently Neutralize Human Cytomegalovirus Infection by Targeting Different Epitopes on the gH/gL/UL128-131A Complex
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DOI：
10.1128/jvi.01809-09
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发表时间：
2010-01-15
影响因子：
5.4
通讯作者：
Lanzavecchia, Antonio
中科院分区：
文献类型：
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作者：
Macagno, Annalisa;Bernasconi, Nadia L.;Lanzavecchia, Antonio
人巨细胞病毒（HCMV）是一种广泛传播的病原体，在免疫功能低下的患者和感染的胎儿中引起严重的疾病。通过使来自HCMV免疫供体的记忆B细胞永生化，我们分离出一组人单克隆抗体，其在极低浓度（90%抑制浓度[IC（90）]值范围为5至200 pM）下中和内皮细胞、上皮细胞和骨髓细胞的HCMV感染。除了与UL 128基因产物中的保守表位结合的抗体之外，所有其他抗体都与需要表达gH/gL/UL 128 - 131 A复合物的两种或更多种蛋白质的构象表位结合。还分离出针对gB、gH或gM/gN的抗体，尽管效力较低，但能够中和内皮-上皮细胞和成纤维细胞的感染。这项研究描述了非常有效的抗HCMV的中和抗体，可用于被动免疫治疗，并确定，通过使用这种抗体，新的抗原靶点HCMV的免疫原的设计，能够引发以前未知的中和抗体反应。
Human cytomegalovirus (HCMV) is a widely circulating pathogen that causes severe disease in immuno-compromised patients and infected fetuses. By immortalizing memory B cells from HCMV-immune donors, we isolated a panel of human monoclonal antibodies that neutralized at extremely low concentrations (90% inhibitory concentration [IC(90)] values ranging from 5 to 200 pM) HCMV infection of endothelial, epithelial, and myeloid cells. With the single exception of an antibody that bound to a conserved epitope in the UL128 gene product, all other antibodies bound to conformational epitopes that required expression of two or more proteins of the gH/gL/UL128-131A complex. Antibodies against gB, gH, or gM/gN were also isolated and, albeit less potent, were able to neutralize infection of both endothelial-epithelial cells and fibroblasts. This study describes unusually potent neutralizing antibodies against HCMV that might be used for passive immunotherapy and identifies, through the use of such antibodies, novel antigenic targets in HCMV for the design of immunogens capable of eliciting previously unknown neutralizing antibody responses.