Antibody neutralization of cytomegalovirus (CMV) entry into diverse cell types is a key consideration for development of vaccines and immunotherapeutics. CMV entry into fibroblasts differs significantly from entry into epithelial or endothelial cells: fibroblast entry is mediated by gB and gH/gL/gO, whereas both epithelial and endothelial cell entry require an additional pentameric complex (PC) comprised of gH/gL/UL128/UL130/UL131A. Because PC-specific antibodies in CMV-seropositive human sera do not affect fibroblast entry but potently block entry into epithelial or endothelial cells, substantially higher neutralizing potencies for CMV-positive sera are observed when assayed using epithelial cells as targets than when using fibroblasts. That certain sera exhibit similar discordances between neutralizing potencies measured using epithelial vs. endothelial cells (Gerna G. et al.J Gen Virol, 89:853–865, 2008) suggested that additional mechanistic differences may also exist between epithelial and endothelial cell entry. To further explore this issue, neutralizing potencies using epithelial and endothelial cells were simultaneously determined for eight CMV-positive human sera, CMV-hyperimmune globulin, and a panel of monoclonal or anti-peptide antibodies targeting specific epitopes in gB, gH, gH/gL, or the PC. No significant differences were observed between epithelial and endothelial neutralizing potencies of epitope-specific antibodies, CMV-hyperimmune globulin, or seven of the eight human sera. However, one human serum exhibited a six-fold higher potency for neutralizing entry into epithelial cells vs. endothelial cells. These results suggest that epitopes exist that are important for epithelial entry but are less critical, or perhaps dispensable, for endothelial cell entry. Their existence should be considered when developing monoclonal antibody therapies or subunit vaccines representing limited epitopes.

中文翻译：

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抗体的比较中和力表明人巨细胞病毒进入上皮和内皮细胞的保守性和机理差异。

巨细胞病毒（CMV）的抗体中和进入多种细胞类型是开发疫苗和免疫疗法的关键考虑因素。CMV进入成纤维细胞与进入上皮或内皮细胞有显着差异：成纤维细胞进入是由gB和gH / gL / gO介导的，而上皮和内皮细胞进入都需要由gH / gL / UL128 /组成的五聚体复合物（PC） UL130 / UL131A。因为在CMV血清反应阳性的人血清中PC特异性抗体不会影响成纤维细胞的进入，但会有效阻止进入上皮或内皮细胞的进入，所以以上皮细胞为靶标进行测定时，与使用成纤维细胞相比，观察到的CMV阳性血清的中和力要高得多。某些血清在使用上皮vs. 内皮细胞（Gerna G.等人，J Gen Virol，89：853-865，2008）表明上皮细胞和内皮细胞进入之间也可能存在其他机制差异。为了进一步探讨这个问题，同时测定了八种CMV阳性人血清，CMV超免疫球蛋白和一组针对gB，gH，gH / gL中特定表位的单克隆或抗肽抗体，使用上皮和内皮细胞的中和力，或PC。在表位特异性抗体，CMV-超免疫球蛋白或八种人类血清中的七种上皮和内皮中和力之间未观察到显着差异。但是，一种人血清中和进入上皮细胞的能力比内皮细胞高六倍。这些结果表明存在对于上皮进入很重要但对于内皮细胞进入而言不太关键或可能不是必需的表位。在开发代表有限表位的单克隆抗体疗法或亚单位疫苗时，应考虑其存在。