Peptides from cytomegalovirus UL130 and UL131 proteins induce high titer antibodies that block viral entry into mucosal epithelial cells.

Peptides from cytomegalovirus UL130 and UL131 proteins induce high titer antibodies that block viral entry into mucosal epithelial cells.
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DOI:
10.1016/j.vaccine.2011.01.079
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发表时间:
2011-03-24
期刊:
影响因子:
5.5
通讯作者:
McVoy, Michael A.
McVoy, Michael A.
中科院分区:
医学3区
文献类型:
--
作者:
Saccoccio, Frances M.;Sauer, Anne L.;Cui, Xiaohong;Armstrong, Amy E.;Habib, El-Sayed E.;Johnson, David C.;Ryckman, Brent J.;Klingelhutz, Aloysius J.;Adler, Stuart P.;McVoy, Michael A.

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巨细胞病毒感染是一种重要的疾病原因,目前还没有获得许可的疫苗。最近的研究集中在gH/gL/UL 128 -131复合物上,因为gH/gL/UL 128 -131的抗体中和病毒进入上皮细胞。先前的研究使用了来自视网膜色素上皮的细胞,而为了防止传播,疫苗诱导的抗体可能需要阻断口腔或生殖器粘膜上皮细胞的病毒感染。我们发现gH/gL/UL 128 -131是病毒有效进入口腔和生殖器粘膜上皮细胞所必需的,来自UL 130和UL 131的短肽在兔中引发高滴度中和抗体,并且此类抗体中和病毒进入源自这些相关组织的上皮细胞。这些结果表明,单个亚基或肽可能足以引起有效的上皮进入中和反应,并且针对这些中和表位的分泌性抗体具有通过阻断初始粘膜感染来提供杀菌免疫的潜力。
Cytomegalovirus infections are an important cause of disease for which no licensed vaccine exists. Recent studies have focused on the gH/gL/UL128-131 complex as antibodies to gH/gL/UL128-131 neutralize viral entry into epithelial cells. Prior studies have used cells from the retinal pigment epithelium, while to prevent transmission, vaccine-induced antibodies may need to block viral infection of epithelial cells of the oral or genital mucosa. We found that gH/gL/UL128-131 is necessary for efficient viral entry into epithelial cells derived from oral and genital mucosa, that short peptides from UL130 and UL131 elicit high titer neutralizing antibodies in rabbits, and that such antibodies neutralize viral entry into epithelial cells derived from these relevant tissues. These results suggest that single subunits or peptides may be sufficient to elicit potent epithelial entry neutralizing responses and that secretory antibodies to such neutralizing epitopes have the potential to provide sterilizing immunity by blocking initial mucosal infection.
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