Cytomegalovirus vaccines fail to induce epithelial entry neutralizing antibodies comparable to natural infection.
Cytomegalovirus vaccines fail to induce epithelial entry neutralizing antibodies comparable to natural infection.
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DOI：
10.1016/j.vaccine.2008.07.092
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发表时间：
2008-10-23
期刊：
影响因子：
5.5
通讯作者：
McVoy MA
中科院分区：
文献类型：
--
作者：
Cui X;Meza BP;Adler SP;McVoy MA
中和巨细胞病毒 (CMV) 进入成纤维细胞的抗体主要针对附着和进入所需的病毒体糖蛋白内的表位。然而，巨细胞病毒进入上皮细胞和内皮细胞的机制与进入成纤维细胞不同。通过同时测量针对 CMV 进入成纤维细胞和上皮细胞的中和活性的测定，我们发现人免疫血清和 CMV 超免疫球蛋白针对上皮细胞进入的中和活性平均比成纤维细胞高 48 倍，这表明天然 CMV 感染会引发上皮进入特异性的中和抗体。重组gB 不能吸附该活性。 Towne 疫苗和 gB/MF59 亚单位疫苗诱导的上皮进入特异性中和活性比自然感染后观察到的平均低 28 倍 (Towne) 或 15 倍 (gB/MF59)。这些结果表明，CMV 疫苗的功效可以通过诱导上皮进入特异性中和抗体来增强。
Antibodies that neutralize cytomegalovirus (CMV) entry into fibroblasts are predominantly directed against epitopes within virion glycoproteins that are required for attachment and entry. However, the mechanism of CMV entry into epithelial and endothelial cells differs from fibroblast entry. Using assays that simultaneously measured neutralizing activities against CMV entry into fibroblasts and epithelial cells, we found that human immune sera and CMV-hyperimmuneglobulins have on average 48-fold higher neutralizing activities against epithelial cell entry compared to fibroblast entry, suggesting that natural CMV infections elicit neutralizing antibodies that are epithelial entry-specific. This activity could not be adsorbed with recombinant gB. The Towne vaccine and the gB/MF59 subunit vaccine induced epithelial entry-specific neutralizing activities that were on average 28-fold (Towne) or 15-fold (gB/MF59) lower than those observed following natural infection. These results suggest that CMV vaccine efficacy may be enhanced by induction of epithelial entry-specific neutralizing antibodies.
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